huntingtin endocytosis

Huntingtin (HTT) is a large intracellular protein with a molecular weight (MW) of 348 kDa, which is functionally involved in diverse cellular processes. Finally, decreased binding between mutant Huntingtin and proteins such as MLK2 (MAP3K10), HIP1, and HIP14 leads to apoptotic cell death, impaired vesicle trafficking, and endocytosis. Mutant huntingtin inhibits clathrin-independent endocytosis and causes accumulation of cholesterol in vitro and in vivo Eugenia Trushina , Raman Deep Singh, Roy B. Dyer, Sheng Cao, Vijay H. Shah , Robert G. Parton, Richard E. Pagano, Cynthia T. McMurray Unexpectedly, mhtt does not inhibit clathrin-dependent endocytosis as was anticipated based on known interacting partners. (2000) identified a homologous cDNA, which they designated Hip12. Huntington's disease (HD) is a progressive neurodegenerative disorder that is caused by abnormal expansion of CAG trinucleotide repeats. We show that the mutant Huntington's disease (HD) protein (mhtt) specifically inhibits endocytosis in primary striatal neurons. The subcellular localisation of huntingtin and many of its interactors suggest a role in endocytosis, and recently it has been shown that huntingtin interacts indirectly with the early endosomal protein Rab5 through HAP40. The HIP1 gene encodes huntingtin interacting protein-1, which is an endocytic protein that colocalizes with the adaptor complex AP2 (see, e.g., AP2A1; 601026) and clathrin to play a role in endocytosis at the plasma membrane of various cells (summary by Metzler et al., 2003). Apparently, it plays a functional role in cytoskeletal assembling, vesicle trafficking, and endocytosis [282–284]. Huntingon's disease is a progressive neurodegenerative disease arising from expansion of a polyglutamine (polyQ) tract in the protein huntingtin (Htt) resulting in aggregation of mutant Htt into nuclear and/or cytosolic inclusions in neurons. Huntingtin-interacting protein family members are evolutionarily conserved from yeast to humans, and they are known to be key factors in clathrin-mediated endocytosis. On the basis of these results, we conclude that abnormal polyglutamine expansion in huntingtin affects clathrin-mediated endocytosis, … CME suppression was … It is reasonable to propose that mutant huntingtin shows aberrant binding to individual interacting partners and, consequently, the function of the specific interacting protein is disrupted. Huntington’s disease (HD) is a genetic disorder that progressively affects an individual's behavioral, cognitive, and motor function. Structural Basis for HIP1 Function in Clathrin Mediated Endocytosis and Huntingto Ybe, Joel A. Indiana University Bloomington, Bloomington, IN, United States. Here is a list of a few concerns. During this process, cargo mol- ecules are clustered and concentrated within the emerging coated pit. It binds to the amino terminus of huntingtin in a region downstream of the polyglutamine sequence that undergoes expansion in Huntington's disease (28). Huntingtin (HTT) is a large (348 kDa) protein that is essential for embryonic development and is involved in diverse cellular activities such as vesicular transport, endocytosis, autophagy and the regulation of transcription. Importantly, this SV endocytosis defect was corrected by overexpression of wild-type huntingtin in homozygous htt(Q140/Q140) neurons. Huntingtin-interacting protein 1. It is believed that accumulation of high levels of the free form of this protein (free as in dissociated from the huntingtin and free to bind other key protein (s)) in the cell is one of the mechanisms by which neuron cell death is caused in Huntington's disease (via the caspase -3 route). Huntingtin-associated protein 1 (HAP1) was initially identified as a binding partner of huntingtin, mutations in which underlie Huntington's disease. In yeast, a functional … Apical progenitors maintain their polarity through endocy-tosis and trafficking from the trans-Golgi network to the plasma membrane at the apical endfeet (19). 17 Thus, the N-terminal huntingtin fragment contain- 1.10.4 The Role of Huntingtin in Endocytosis 21 1.10.5 The Role of Huntingtin in Synaptic Transmission 22 1.10.6 The Role of Huntingtin in the Cell Stress Response 23 1.11 The Pathogenic Threshold for HD 25 1.12 Polyglutamine Flanking Sequences 26 1.12.1 The Rusty Hinge Hypothesis 29 1.13 Pathogenic Mechanisms in HD 31 1.13.1 Excitotoxicity in HD 31 1.13.2 Mitochondrial Dysfunction … Huntington disease is an adult onset neurodegenerative disease characterized by motor, cognitive, and psychiatric dysfunction, caused by a CAG expansion in the HTT gene. Huntington's disease (HD) is a late-onset neurodegenerative genetic disorder that produces uncontrolled physical movements, devastates intellectual faculties and triggers emotional disturbances. Prion-like transmission of these aggregates between cells has been demonstrated. Yet in spite of the clear genetic … Systems biology study of factors leading to perturbed endocytosis in Huntington's Disease This project, funded by the CHDI foundation, is focusing on Huntington’s Disease (HD), a neurodegenerative disorder caused by mutant Huntingtin (mHtt) that impairs cognitive capacity and causes motor deficits along with involuntary movements. Wild-type htt is predominantly cytoplasmic and probably functions in vesicle transport, cytoskeletal anchoring, clathrin-mediated endocytosis, neuronal transport or … We observe unique spreading patte rns when huntingtin is expressed in different populations of neurons, supporting the idea that nearby cells and neuronal circuits are likely targets of spreading. The actin cytoskeleton has been implicated in endocytosis, yet few molecules that link these systems have been identified. Abstract. The Htt protein is involved in vesicle trafficking as it interacts with HIP1 to mediate endocytosis. The encoded protein binds to the huntingtin protein in the brain; this interaction is lost in Huntington's disease. They are associated with each other, the interacting site is the 371-599 of HAP1. Loss of huntingtin function slows synaptic vesicle endocytosis in striatal neurons from the httQ140/Q140 mouse model of Huntington's disease. went looking for Rab5 effector proteins by affinity chromatography, they isolated HAP40 and Htt. The shaky movements of people with Huntington's disease are caused by death of a specific group of nerve cells. Huntington disease, HIP1, huntingtin-interacting protein 1, mutation, clathrin, endocytosis: Informations complémentaires: This research was originally published in The Journal of Biological Chemistry. 10 :1807-1817. Endocytosis is a basic cellular process that has been conserved and adapted from single cell eukaryotes through humans (reviewed in Mellman 1996; Mukherjee et al. Although the Huntington protein (Htt) is ubiquitously expressed, expansion of the poly-glutamine tract in Htt leads to the progressive loss of specific neuronal subpopulations in HD brains. However, The molecular chaperones Hsp70 and Hsp40 promote the folding of newly synthesized huntingtin (htt) into a native structure. Read "HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis, Human Molecular Genetics" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. From NCBI Gene: The product of this gene is a membrane-associated protein that functions in clathrin-mediated endocytosis and protein trafficking within the cell. We observe unique spreading patterns when huntingtin is expressed in different populations of neurons, supporting the idea that nearby cells and neuronal circuits are likely targets of spreading. Abbreviations used: AMPA, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid; ANTH, AP180 N-terminal homology; CME, clathrin-mediated endocytosis; EGF, epidermal growth factor; HIP1, huntingtin-interacting protein 1; HIP1R, HIP1-related; NMDA, N -methyl- D -aspartate; siRNA, small interfering RNA. Huntingtin mutation leads to aggregate sequestration of various proteins, including transcription factors. 205 (8): 1869–77. 1 Correspondence may be addressed to either of these authors (email … This decreased receptor-mediated endocytosis, measured by the internalization of transferrin in the mutated cells. 134: 104637 (2020). Huntingtin mutation leads to aggregate sequestration of various proteins, including transcription factors. After coat assembly and membrane invagination, which is facilitated by BAR domain-containing proteins, vesicle fission is catalyzed by the recruitment and … Huntingtin (HTT) is a large intracellular protein with a molecular weight (MW) of 348 kDa, which is functionally involved in diverse cellular processes. HAP40 mediates the recruitment of Htt by Rab5 onto early endosomes. HIP1 has also been implicated in the pathogenesis of Huntington's disease. Huntingtin upregulates the expression of Brain Derived Neurotrophic Factor (BDNF) at the transcription level but the mechanism by which huntingtin regulated gene expression has not been determined. Huntingtin is a cytoplasmic protein of unknown function that associates with vesicle membranes and microtubules. As a model organism, the fruit fly Drosophila melanogaster has many … The Huntingtin Interacting Protein HIP1 is a Clathrin and α–adaptin-binding Protein Involved in Receptor Mediated Endocytosis. Although no cure exists, scientific research aimed at finding effective treatments for HD is underway. polyQ stretch in this segment of mutant huntingtin (mhtt) shows similar kind of disruption in endocytosis as the full length pro-tein.16 Full-length mhtt deletion mutants, lacking N-terminal domains interacting with HAP1 or dyein, show disrupted vesicu-lar transport. Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors ... antigen presentation, pathogen internalization, and maintenance of plasma membrane surface area. The neurodegeneration in HD is also caused by aberrant immune response in the presence … There are shared regions in HIP1 and HIP12/1R that mediate the binding of clathrin, but there are also sites that are Many of the known huntingtin-binding proteins have roles in endocytosis, whereas comparatively few are involved in exocytosis. On page 605, Pal et al. Hip-1 is a protein that interacts with the huntingtin protein. Huntingtin also affects neuronal stability because its deletion in mice causes degeneration of axon fibers . Cloning and Expression Various evidence has converged to indicate that wild-type huntingtin may be involved in cellular vesicle trafficking, endocytosis, and synaptic function. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors ... antigen presentation, pathogen internalization, and maintenance of plasma membrane surface area. ↑ Björkqvist M, Wild EJ, Thiele J, et al. neuronal loss is prevented by block ing endocytosis, suggesting that spreading requires active interna lization of the pathogenic protein. The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis. The protein (August 2008). J. Exp. The clathrin pathway is a well-established mechanism of the internalization of pathogens, nutrients, various growth factors, and neurotransmitters. Therefore, we have identified an activity-dependent and striatum-specific signature of presynaptic dysfunction in neurons derived from pre-symptomatic HD mice, which is due to loss of wild-type huntingtin function. In HD, both endocytosis and Golgi-membrane trafficking are dysregulated . Recently, we found that Htt is important for the activation of Rab11, a GTPase involved in endosomal recycling. Huntingtin Huntington´s disease Endocytosis: Fecha de publicación: 2013: Editor: Academic Press: Citación: Experimental Neurology 241: 75- 83 (2013) Resumen: Clathrin-mediated endocytosis plays an important role in the maintenance of neuronal integrity in the synaptic terminals. Rat Huntingtin (Htt) ELISA Kit from Assay Genie is a pre-coated immunoassay with a range ofRat Huntingtin (Htt) ELISA Kit and has been designed to measure Rat Huntingtin (Htt) in serum, plasma & cell culture supernatant samples. Cell Signal. Neuroinflammation is a typical feature of most neurodegenerative diseases that leads to an array of pathological changes within the affected areas in the brain. Huntingtin-interacting protein 1 (HIP1)1 was identified through its binding to the N-terminal domain of huntingtin, a region containing a polymorphic stretch of glutamine residues (1, 2). Mackenzie KD , Lim Y , Duffield MD , Chataway T , Zhou XF , Keating DJ Huntingtin-associated protein 1 (HAP1) was initially identified as a binding partner of huntingtin, mutations in which underlie Huntington's disease. Its protein interactions suggest that huntingtin … Studies on subcellular localization and identification of normal partners suggest that htt could function in vesicular trafficking and endocytosis (2). Clathrin-mediated endocytosis begins with coat nucleation mediated by cargo and phosphatidylinositol(4,5)-bisphosphate, PI(4,5)P 2. The important point here would seem to be that huntingtin inhibits caveolar-related endocytosis. In this study, the effects of HIP1 on the degradation of EGFR, which have important roles in carcinogenesis after EGF stimulation, were examined. The encoded protein binds to the huntingtin protein in the brain; this interaction is lost in Huntington's disease. (from RefSeq NM_005338) RefSeq Summary (NM_005338): The product of this gene is a membrane-associated protein that functions in clathrin-mediated endocytosis and protein trafficking within the cell. Endocytosis occurs via several distinct pathways and requires coordinated interactions between a variety of molecules at the membrane and cell cortex. Alternative splicing results in multiple transcript variants. huntingtin-interacting proteins that might be associ-ated with the normal function of huntingtin and/or involved in the pathology of Huntington’s disease. Second, clathrin-mediated endocytosis was disrupted specifically in striatal neurons and only during elevated activity. Therefore, we have identified an activity-dependent and striatum-specific signature of presynaptic dysfunction in neurons derived from pre-symptomatic HD mice, which is due to loss of wild-type huntingtin function. Search 12 grants from Joel Ybe Search grants from Indiana University Bloomington. Huntingtin also plays an important role in the … Instead, inhibition occurs through a non-clathrin, caveolar-related pathway. Huntington disease (HD) is an autosomal dominant, adult onset, progressive neurodegenerative disease; it is characterized by the triad of abnormal movements (typically chorea), cognitive impairment, and psychiatric illness. After screening 17 cell lines, the coexpression of HIP1 and EGFR was detected in HeLa cells. ese include endocytosis, vesicle transport, autophagy, and transcriptional regulation [1]. Huntingtin (HTT) is a large intracellular protein with a molecular weight (MW) of 348 kDa, which is func-tionally involved in diverse cellular processes. Mutant huntingtin impairs endosome secretion and recycling. Here we studied fibroblasts of healthy individuals and patients with Huntington's disease (HD), which is a movement disorder caused by polyglutamine expansion in Htt. In this study, the interaction between HAP1 and Sec23A was also … Hum Mol Genet 2001. Huntington-interacting protein 1 (HIP1) is associated with various tumor types; however, its precise functions in tumor cells are unclear. Instead, inhibition occurs through a non-clathrin, caveolar-related pathway. Huntingtin-associated protein-1 (HAP1) regulates endocytosis and interacts with multiple trafficking-related proteins. Download PDF of article text and main figures. Huntingtin (HTT), the protein mutated in Huntington disease, acts as a molecular scaffold and promotes intracellular dynamics. It was initially identified through a yeast two-hybrid screen as a binding partner of huntingtin (Kalchman et al., In this study, we have identified Htt-associated protein 40 (HAP40) as a novel effector of the small guanosine triphosphatase Rab5, a key regulator of endocytosis. It binds to the amino terminus of huntingtin in a region down-stream of the polyglutamine sequence that undergoes expan-sion in Huntington’s disease (28). Mol. The N-terminal portion of Htt contains a stretch of glutamines ... anchoring to the cytoskeleton, clathrin-mediated endocytosis, postsynaptic signaling, transcriptional regulation and anti-apoptotic functions (Gil and Rego, 2008; Imarisio et al., 2008). Tel: +44 24 76 52 2 461; Fax: +44 024 76 52 3 568; E-mail: corinne.smith@warwick.ac.uk. The increase of SCAMP5 impairs endocytosis, which in turn enhances mtHTT aggregation. When Pal et al. Huntingtin-interacting protein-1 (HIP1; 601767) is a membrane-associated protein that interacts with huntingtin (HTT; 613004), the protein altered in Huntington disease (HD; 143100).While attempting to isolate the mouse homolog of HIP1, Chopra et al. Interacts (via ANK repeats) with CLIP3 (PubMed:26198635, PubMed:28882895). In this article, we focus on the potential roles of huntingtin– protein interactions in the pathogenesis of Huntington’s disease. BRITE hierarchy: Genes: HSA: 9026(HIP1R) PTR: 100613620(HIP1R) PPS: 100985393(HIP1R) GGO: 101144413(HIP1R) PON: 100172029(HIP1R) NLE: 100586033(HIP1R) … In line with a physiological function of the HAP1-clathrin interaction this study detected a dramatic reduction in vesicle retrieval and endocytosis in adrenal chromaffin cells. Huntington's disease (HD) is caused by CAG repeat expansion within the HTT gene, with the dysfunction and eventual loss of striatal medium spiny neurons a notable feature. Vesicular trafficking can either be clathrin mediated or clathrin independent. In addition to its possible involvement in endocytosis, HIP1 may play a role in the pathogenesis of Huntington's disease. Huntingtin-interacting protein 1 (HIP1) and its relative, HIP12/1R, contribute to the budding of clathrin-coated vesicles (CCVs) [1, 2]. However, huntingtin deficient embryos do not display obvious visceral endoderm defects, with the notable exception of compromised iron transport in later stage mutants, although iron uptake is undisturbed and endocytosis is not impaired in huntingtin deficient embryos or embryonic stem cells [16, 18]. K20040 HIP1R, SLA2; huntingtin-interacting protein 1-related protein Membrane trafficking [BR:ko04131] Endocytosis Clathrin-mediated endocytosis Others K20040 HIP1R, SLA2; huntingtin-interacting protein 1-related protein. Pal A., Severin F., Lommer B., Shevchenko A., Zerial M. The molecular mechanisms underlying the targeting of Huntingtin (Htt) to endosomes and its multifaceted role in endocytosis are poorly understood. Huntington's disease (HD) is caused by a mutated form of the huntingtin gene, where excessive (more than 36) CAG repeats result in formation of an unstable protein. These expanded repeats lead to production of a huntingtin protein that contains an abnormally long polyglutamine tract at the N-terminus. A mutation in exon 1 of … It is important in the generation of clathrin coated vesicles in the neuron. Huntingtin-interacting protein 1 (HIP1) is an important link between the actin cytoskeleton and clathrin-mediated endocytosis machinery. Actin polymerization is not absolutely required for clathrin-mediated endocytosis, and disruption of actin does not interfere with the early stages of clathrin-coated pit formation. Moreover, their observations that the pathogenic huntingtin aggregates are spread from ORNs to glia and PNs of the olfactory system in a prion-like manner is very interesting. Hum Mol Genet. Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain. The molecular mechanisms underlying the targeting of Huntingtin (Htt) to endosomes and its multifaceted role in endocytosis are poorly understood. In this gene, the DNA base sequence cytosine-adenine-guanine is repeated multiple times. Our findings demonstrate that HIP1 is a novel component of the endocytic machinery. Huntingtin. The mass of huntingtin protein is dependent largely on the number of glutamine residues it has, the predicted mass is around 350 kDa. Normal huntingtin is generally accepted to be 3144 amino acids in size. The exact function of this protein is not known, but it plays an important role in nerve cells. * Corresponding author. Instead, inhibition occurs through a non-clathrin, caveolar-related pathway. Huntington’s disease (HD) is a genetically domi-nant neurodegenerative condition caused by an unique muta-tion in the disease gene huntingtin. Huntingtin-HAP40 complex is a novel Rab5 effector that regulates early endosome motility and is up-regulated in Huntington's disease. By the same token, huntingtin shuttles through the nucleus, where it is required for proper nuclear localiza-tion of its transcription factor partners, suggesting that huntingtin may play a role in transcription cascades in HIP1 (Huntingtin-interacting protein 1) protects normal neurological tissue from erroneous inflammatory and apoptotic events by linking the actin cytoskeleton and clathrin-mediated endocytosis machinery. This review describes recent advances in understanding synaptic dysfunction in HD. Most data suggest that polyglutamine-mediated aggregation associated with expression of mutant huntingtin protein (mhtt) contributes to the pathology. A defective HTT (huntingtin) gene directly causes to the developmental pathology of We observe unique spreading patte rns when huntingtin is expressed in different populations of neurons, supporting the idea that nearby cells and neuronal circuits are likely targets of spreading. Interacts (via ANK repeats) with HTT; this interaction is inversely correlated to the length of the polyglutamine tract added to the huntingtin protein in Huntington disease … Abstract. Huntingtin-interacting protein 1 (HIP1) was initially described as an adaptor protein associated with the clathrin light chain and AP2 adaptor complex with a role in clathrin-mediated endocytosis having been first identified in a yeast two-hybrid screen for interacting partners of huntingtin, which is encoded by the huntingtin chorea gene, a gene which when mutated causes Huntington's disease. Huntingtin-interacting protein 1 also known as HIP-1 is a protein that in humans is encoded by the HIP1 gene. HAP1 and APP are highly colocalized in a number of brain regions, with similar distribution patterns in both mouse and human brains. Description: Homo sapiens huntingtin interacting protein 1 (HIP1), transcript variant 1, mRNA. Here, we have cloned and characterized mHip1R, a protein that is closely related to huntingtin interacting protein 1 (Hip1). Importantly, this SV endocytosis defect was corrected by overexpression of wild-type huntingtin in homozygous htt(Q140/Q140) neurons. 10 :1807-1817. Neurobiol Dis . Huntingtin facilitates dynein/dynactin-mediated vesicle transport.. Proc Natl Acad Sci USA 104, 10045-10050. 10 (17): 1807–17. Huntington’s disease (HD) is the most prevalent disorder Mackenzie KD , Lim Y , Duffield MD , Chataway T , Zhou XF , Keating DJ . Altered interactions of mutant huntingtin with its associated partners could contribute to abnormal synaptic transmission in HD. This raises the possibility that normal huntingtin encounters some elements of the endocytosis machinery on the regular basis, and only upon expansion of polyQ it is committed to aggregation by the same machinery. Finally, decreased binding between mutant Huntingtin and proteins such as MLK2 (MAP3K10), HIP1, and HIP14 leads to apoptotic cell death, impaired vesicle trafficking and endocytosis. However, We show that the mutant Huntington's disease (HD) protein (mhtt) specifically inhibits endocytosis in primary striatal neurons. Here we identified the Caenorhabditis elegans protein huntingtin-interacting protein-related 1 (HIPR-1) as a host factor essential for Orsay virus infec-tion of C. elegans. Links Mutant huntingtin inhibits clathrin-independent endocytosis and causes accumulation of cholesterol in vitro and in vivo.Trushina E, Singh RD, Dyer RB, Cao S, Shah VH, Parton RG, Pagano RE, McMurray CT. 2006 Dec 15;15(24):3578-91. 11532990 Mutant huntingtin has been previously shown to interact with clathrin, which is a major protein involved in endocytosis. These include endocytosis, vesicle transport, autophagy, and transcriptional regulation . The data may explain why vesicle motility is disrupted in Htt mutant cells. Expression of SCAMP5 is markedly increased in the striatum of Huntington disease patients and is induced in cultured striatal neurons by endoplasmic reticulum (ER) stress or by mtHTT. Huntingtin is a cytoplasmic protein of unknown function that associates with vesicle membranes and microtubules. Huntingtin (HTT) is an essential protein during early embryogenesis and the development of the central nervous system (CNS). Abstract. neuronal loss is prevented by block ing endocytosis, suggesting that spreading requires active interna lization of the pathogenic protein. Huntington disease (HD) is caused by a polyglutamine-expansion mutation in huntingtin (HTT) that makes the protein toxic and aggregate-prone. 14:00 14:10 Understanding the effect of Huntingtin aggregates on clathrin-mediated endocytosis Surya Bansi Singh, National Centre For cell Science, India 14:10 14:30 Q&A Chair: Helene Plun-Favreau Moderator: Patrick Lewis 14:30 14:40 Break 14:40 15:10 Lightning talks followed by a poster session 15:10 16:30 Session 4: Mitochondrial biology [20] Thomas EA , Coppola G , Tang B , Kuhn A , Kim S , Geschwind DH , et al. Mutant huntingtin inhibits clathrin-independent endocytosis and causes accumulation of cholesterol in vitro and in vivo By Raman Singh and Sheng Cao PACSIN 1 interacts with huntingtin and is absent from synaptic varicosities in presymptomatic Huntington's disease brains 11063258: HIP12 is a non-proapoptotic member of a gene family including HIP1, an interacting protein with huntingtin. HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis Med. CONICET Digital, el repositorio institucional del CONICET, un servicio gratuito para acceder a la producción científico-tecnológica de investigadores, becarios y demás personal del CONICET. HTT associates with vesicles and microtubules. Hum Mol Genet 2001. The yeast homolog of HIP1, sla2p, is required for the development of CCVs in yeast [3, 4]. Apical progenitors maintain their polarity through endocytosis and the trafficking of proteins from the trans-Golgi network to the plasma membrane at the apical endfeet . This neuronal loss is prevented by blocking endocytosis, suggesting that spreading requires active internalization of the pathogenic protein. One culprit — the mutant huntingtin protein — is … Furthermore, through examination of transferrin endocytosis in HAP1-/-cortical neurons, this study has determined that HAP1 regulates neuronal endocytosis. Accumulation of expanded polyglutamine proteins is considered to be a major pathogenic biomarker of Huntington disease. AIMS: The aggregation of Huntingtin (HTT) protein and of its moiety encoded by its Exon1 (HTTExon1) into fibrillar structures inside neurons is the molecular hallmark of Huntington's disease. 11517213: HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and adaptor protein 2. Normal huntingtin interacts with various cytoskeletal and synaptic vesicle proteins that are essential for exocytosis and endocytosis. By screening a human frontal cortex cDNA library with an EST that … ... endocytosis, post-synaptic signaling, and cell survival pathways. Crossref, Medline, Google Scholar; Caviston JP, Ross JL, Antony SM, Tokito M, Holzbaur EL (2007). Huntington's disease is associated with mutants of the gene, which codes for the protein huntingtin. Subcellular localization and protein interaction data indicate that HAP1 may be important in vesicle trafficking, cell signalling and receptor internalization. Although polyglutamine [poly(Q)] expansion, the causative mutation in Huntington disease (HD) was discovered several years ago, there is as yet no proven mechanism for the selective vulnerability of neurons in the striatum and cortex observed in the disease. Huntington’s disease (HD) is a fatal neurodegenerative disorder that primarily targets medium spiny neurons, leading to the gradual atrophy of the striatum.

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