Unconventional Secretion and Intercellular Transfer of Mutant Huntingtin

The mechanism of intercellular transmission of pathological agents in neurodegenerative diseases has received much recent attention. Huntington’s disease (HD) is caused by a monogenic mutation in the gene encoding Huntingtin (HTT). Mutant HTT (mHTT) harbors a CAG repeat extension which enc...

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Main Author: Bor Luen Tang
Format: Article
Language:English
Published: MDPI AG 2018-06-01
Series:Cells
Subjects:
Online Access:http://www.mdpi.com/2073-4409/7/6/59
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spelling doaj-ec94b58534254943978881ba7f5b39bd2020-11-25T00:26:18ZengMDPI AGCells2073-44092018-06-01765910.3390/cells7060059cells7060059Unconventional Secretion and Intercellular Transfer of Mutant HuntingtinBor Luen Tang0Department of Biochemistry, Yong Loo Lin School of Medicine, 117597 Singapore, SingaporeThe mechanism of intercellular transmission of pathological agents in neurodegenerative diseases has received much recent attention. Huntington’s disease (HD) is caused by a monogenic mutation in the gene encoding Huntingtin (HTT). Mutant HTT (mHTT) harbors a CAG repeat extension which encodes an abnormally long polyglutamine (polyQ) repeat at HTT’s N-terminus. Neuronal pathology in HD is largely due to the toxic gain-of-function by mHTT and its proteolytic products, which forms both nuclear and cytoplasmic aggregates that perturb nuclear gene transcription, RNA splicing and transport as well cellular membrane dynamics. The neuropathological effects of mHTT have been conventionally thought to be cell-autonomous in nature. Recent findings have, however, indicated that mHTT could be secreted by neurons, or transmitted from one neuronal cell to another via different modes of unconventional secretion, as well as via tunneling nanotubes (TNTs). These modes of transmission allow the intercellular spread of mHTT and its aggregates, thus plausibly promoting neuropathology within proximal neuronal populations and between neurons that are connected within neural circuits. Here, the various possible modes for mHTT’s neuronal cell exit and intercellular transmission are discussed.http://www.mdpi.com/2073-4409/7/6/59Huntingtin (HTT)Huntington’s disease (HD)membrane trafficpolyglutamine (polyQ) tracttunneling nanotube (TNT)unconventional secretion
collection DOAJ
language English
format Article
sources DOAJ
author Bor Luen Tang
spellingShingle Bor Luen Tang
Unconventional Secretion and Intercellular Transfer of Mutant Huntingtin
Cells
Huntingtin (HTT)
Huntington’s disease (HD)
membrane traffic
polyglutamine (polyQ) tract
tunneling nanotube (TNT)
unconventional secretion
author_facet Bor Luen Tang
author_sort Bor Luen Tang
title Unconventional Secretion and Intercellular Transfer of Mutant Huntingtin
title_short Unconventional Secretion and Intercellular Transfer of Mutant Huntingtin
title_full Unconventional Secretion and Intercellular Transfer of Mutant Huntingtin
title_fullStr Unconventional Secretion and Intercellular Transfer of Mutant Huntingtin
title_full_unstemmed Unconventional Secretion and Intercellular Transfer of Mutant Huntingtin
title_sort unconventional secretion and intercellular transfer of mutant huntingtin
publisher MDPI AG
series Cells
issn 2073-4409
publishDate 2018-06-01
description The mechanism of intercellular transmission of pathological agents in neurodegenerative diseases has received much recent attention. Huntington’s disease (HD) is caused by a monogenic mutation in the gene encoding Huntingtin (HTT). Mutant HTT (mHTT) harbors a CAG repeat extension which encodes an abnormally long polyglutamine (polyQ) repeat at HTT’s N-terminus. Neuronal pathology in HD is largely due to the toxic gain-of-function by mHTT and its proteolytic products, which forms both nuclear and cytoplasmic aggregates that perturb nuclear gene transcription, RNA splicing and transport as well cellular membrane dynamics. The neuropathological effects of mHTT have been conventionally thought to be cell-autonomous in nature. Recent findings have, however, indicated that mHTT could be secreted by neurons, or transmitted from one neuronal cell to another via different modes of unconventional secretion, as well as via tunneling nanotubes (TNTs). These modes of transmission allow the intercellular spread of mHTT and its aggregates, thus plausibly promoting neuropathology within proximal neuronal populations and between neurons that are connected within neural circuits. Here, the various possible modes for mHTT’s neuronal cell exit and intercellular transmission are discussed.
topic Huntingtin (HTT)
Huntington’s disease (HD)
membrane traffic
polyglutamine (polyQ) tract
tunneling nanotube (TNT)
unconventional secretion
url http://www.mdpi.com/2073-4409/7/6/59
work_keys_str_mv AT borluentang unconventionalsecretionandintercellulartransferofmutanthuntingtin
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