NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being?

Much confusion surrounds the physiological function of the cellular prion protein (PrPC). It is, however, anticipated that knowledge of its function will shed light on its contribution to neurodegenerative diseases and suggest ways to interfere with the cellular toxicity central to them. Consequentl...

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Main Authors:	Mehrabian, Mohadeseh, Hildebrandt, Herbert, Schmitt-Ulms, Gerold
Format:	Online
Language:	English
Published:	SAGE Publications 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122176/

id	pubmed-5122176
recordtype	oai_dc
spelling	pubmed-51221762016-11-29 NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being? Mehrabian, Mohadeseh Hildebrandt, Herbert Schmitt-Ulms, Gerold Review Much confusion surrounds the physiological function of the cellular prion protein (PrPC). It is, however, anticipated that knowledge of its function will shed light on its contribution to neurodegenerative diseases and suggest ways to interfere with the cellular toxicity central to them. Consequently, efforts to elucidate its function have been all but exhaustive. Building on earlier work that uncovered the evolutionary descent of the prion founder gene from an ancestral ZIP zinc transporter, we recently investigated a possible role of PrPC in a morphogenetic program referred to as epithelial-to-mesenchymal transition (EMT). By capitalizing on PrPC knockout cell clones in a mammalian cell model of EMT and using a comparative proteomics discovery strategy, neural cell adhesion molecule-1 emerged as a protein whose upregulation during EMT was perturbed in PrPC knockout cells. Follow-up work led us to observe that PrPC regulates the polysialylation of the neural cell adhesion molecule NCAM1 in cells undergoing morphogenetic reprogramming. In addition to governing cellular migration, polysialylation modulates several other cellular plasticity programs PrPC has been phenotypically linked to. These include neurogenesis in the subventricular zone, controlled mossy fiber sprouting and trimming in the hippocampal formation, hematopoietic stem cell renewal, myelin repair and maintenance, integrity of the circadian rhythm, and glutamatergic signaling. This review revisits this body of literature and attempts to present it in light of this novel contextual framework. When approached in this manner, a coherent model of PrPC acting as a regulator of polysialylation during specific cell and tissue morphogenesis events comes into focus. SAGE Publications 2016-11-22 /pmc/articles/PMC5122176/ /pubmed/27879349 http://dx.doi.org/10.1177/1759091416679074 Text en © The Author(s) 2016 http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mehrabian, Mohadeseh Hildebrandt, Herbert Schmitt-Ulms, Gerold
spellingShingle	Mehrabian, Mohadeseh Hildebrandt, Herbert Schmitt-Ulms, Gerold NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being?
author_facet	Mehrabian, Mohadeseh Hildebrandt, Herbert Schmitt-Ulms, Gerold
author_sort	Mehrabian, Mohadeseh
title	NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being?
title_short	NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being?
title_full	NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being?
title_fullStr	NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being?
title_full_unstemmed	NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being?
title_sort	ncam1 polysialylation: the prion protein's elusive reason for being?
description	Much confusion surrounds the physiological function of the cellular prion protein (PrPC). It is, however, anticipated that knowledge of its function will shed light on its contribution to neurodegenerative diseases and suggest ways to interfere with the cellular toxicity central to them. Consequently, efforts to elucidate its function have been all but exhaustive. Building on earlier work that uncovered the evolutionary descent of the prion founder gene from an ancestral ZIP zinc transporter, we recently investigated a possible role of PrPC in a morphogenetic program referred to as epithelial-to-mesenchymal transition (EMT). By capitalizing on PrPC knockout cell clones in a mammalian cell model of EMT and using a comparative proteomics discovery strategy, neural cell adhesion molecule-1 emerged as a protein whose upregulation during EMT was perturbed in PrPC knockout cells. Follow-up work led us to observe that PrPC regulates the polysialylation of the neural cell adhesion molecule NCAM1 in cells undergoing morphogenetic reprogramming. In addition to governing cellular migration, polysialylation modulates several other cellular plasticity programs PrPC has been phenotypically linked to. These include neurogenesis in the subventricular zone, controlled mossy fiber sprouting and trimming in the hippocampal formation, hematopoietic stem cell renewal, myelin repair and maintenance, integrity of the circadian rhythm, and glutamatergic signaling. This review revisits this body of literature and attempts to present it in light of this novel contextual framework. When approached in this manner, a coherent model of PrPC acting as a regulator of polysialylation during specific cell and tissue morphogenesis events comes into focus.
publisher	SAGE Publications
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122176/
_version_	1613740112178315264

NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being?

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