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Protein fucosylation regulates synapsin Ia/Ib expression and neuronal morphology in primary hippocampal neurons

Murrey, Heather E. and Gama, Cristal I. and Kalividouris, Stacey A. and Luo, Wen-I. and Driggers, Edward M. and Porton, Barbara and Hsieh-Wilson, Linda C. (2006) Protein fucosylation regulates synapsin Ia/Ib expression and neuronal morphology in primary hippocampal neurons. Proceedings of the National Academy of Sciences of the United States of America, 103 (1). pp. 21-26. ISSN 0027-8424. PMCID PMC1324972. http://resolver.caltech.edu/CaltechAUTHORS:MURpnas06

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Abstract

Although fucose-{alpha}(1-2)-galactose [Fuc{alpha}(1-2)Gal] carbohydrates have been implicated in cognitive processes such as long-term memory, the molecular mechanisms by which these sugars influence neuronal communication are not well understood. Here, we present molecular insights into the functions of Fuc{alpha}(1-2)Gal sugars, demonstrating that they play a role in the regulation of synaptic proteins and neuronal morphology. We show that synapsins Ia and Ib, synapse-specific proteins involved in neurotransmitter release and synaptogenesis, are the major Fuc{alpha}(1-2)Gal glycoproteins in mature cultured neurons and the adult rat hippocampus. Fucosylation has profound effects on the expression and turnover of synapsin in cells and protects synapsin from degradation by the calcium-activated protease calpain. Our studies suggest that defucosylation of synapsin has critical consequences for neuronal growth and morphology, leading to stunted neurite outgrowth and delayed synapse formation. We also demonstrate that Fuc{alpha}(1-2)Gal carbohydrates are not limited to synapsin but are found on additional glycoproteins involved in modulating neuronal architecture. Together, our studies identify important roles for Fuc{alpha}(1-2)Gal sugars in the regulation of neuronal proteins and morphological changes that may underlie synaptic plasticity.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.0503381102DOIArticle
http://www.pnas.org/content/103/1/21.longPublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1324972/PubMed CentralArticle
http://www.pnas.org/content/103/1/21.long?tab=dsPublisherSupporting Information
http://dx.doi.org/10.1073/iti0106103Featured InPNAS: This Week in PNAS
http://dx.doi.org/10.1126/stke.3172006tw472Featured InScience Signaling: Editors' Choice
http://dx.doi.org/10.1038/nchembio0206-67Featured InNature Chemical Biology: News and Views
ORCID:
AuthorORCID
Hsieh-Wilson, Linda C.0000-0001-5661-1714
Additional Information:Edited by Pietro De Camilli, Boyer Center for Molecular Medicine, New Haven, CT, and approved November 15, 2005 (received for review April 24, 2005). Published online before print December 22, 2005, 10.1073/pnas.0503381102 We thank Drs. H. T. Kao, T. E. Wilson, and S. B. Ficarro for assistance and helpful discussions. This research was supported by National Institutes of Health Grants R01 NS045061 (to L.C.H.-W. and C.I.G.) and R01 MH070898 (to B.P.), National Institutes of Health Training Grants T32 GM08501 (to C.I.G.) and T32 GM07616 (to H.E.M.), and the Alfred P. Sloan Foundation. Conflict of interest statement: No conflicts declared. This paper was submitted directly (Track II) to the PNAS office.
Funders:
Funding AgencyGrant Number
NIHR01 NS045061
NIHR01 MH070898
NIH Predoctoral FellowshipT32 GM08501
NIH Predoctoral FellowshipT32 GM07616
Alfred P. Sloan FoundationUNSPECIFIED
Subject Keywords:fucose; glycosylation; neurite outgrowth; glycoprotein; calpain
PubMed Central ID:PMC1324972
Record Number:CaltechAUTHORS:MURpnas06
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:MURpnas06
Alternative URL:http://dx.doi.org/10.1073/pnas.0503381102
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5986
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:10 Nov 2006
Last Modified:07 Nov 2017 22:33

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