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Published January 3, 2006 | Published
Journal Article Open

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


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.

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.

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