Nesca, a novel neuronal adapter protein, links the molecular motor kinesin with the pre-synaptic membrane protein, syntaxin-1, in hippocampal neurons

J. Neurochem. (2012) 121, 861–880. Vesicular transport in neurons plays a vital role in neuronal function and survival. Nesca is a novel protein that we previously identified and herein describe its pattern of expression, subcellular localization and protein–protein interactions both in vitro and in...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of neurochemistry Vol. 121; no. 6; pp. 861 - 880
Main Authors:	MacDonald, James I. S., Dietrich, Alfonso, Gamble, Sarah, Hryciw, Todd, Grant, Robert Ian, Meakin, Susan O.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-06-2012 Wiley-Blackwell
Subjects:	Adaptor Proteins, Signal Transducing - metabolism Adaptor Proteins, Vesicular Transport - metabolism Ageing, cell death Animals Biological and medical sciences Blotting, Western Cell physiology Cells Central nervous system Central neurotransmission. Neuromudulation. Pathways and receptors Cytoskeletal Proteins - metabolism Cytoskeleton - metabolism Fundamental and applied biological sciences. Psychology hippocampal neurons Hippocampus - metabolism Humans Immunohistochemistry Immunoprecipitation kinesin Kinesin - metabolism Membranes Mice Molecular and cellular biology Molecular biology molecular transport Nesca Neurochemistry Neurogenesis - physiology Neurons Neurons - metabolism Post-Synaptic Density - metabolism Protein Transport - physiology Proteins SNAREs Synaptic Membranes - metabolism Syntaxin 1 - metabolism syntaxin-1 Transfection Vertebrates: nervous system and sense organs Nesca molecular transport Membrane protein SNARE protein SNAP protein Synaptic membrane Interaction Biological transport kinesin Central nervous system In vitro Survival hippocampal neurons Encephalon syntaxin-1 Syntaxin Neuron Actin SNAREs Cytoskeleton Microtubule Localization Hippocampus
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	J. Neurochem. (2012) 121, 861–880. Vesicular transport in neurons plays a vital role in neuronal function and survival. Nesca is a novel protein that we previously identified and herein describe its pattern of expression, subcellular localization and protein–protein interactions both in vitro and in vivo. Specifically, a large proportion of Nesca is in tight association with both actin and microtubule cytoskeletal proteins. Nesca binds to F‐actin, microtubules, βIII and acetylated α‐tubulin, but not neurofilaments or the actin‐binding protein drebrin, in in vitro‐binding assays. Nesca co‐immunoprecipitates with kinesin heavy chain (KIF5B) and kinesin light‐chain motors as well as with the synaptic membrane precursor protein, syntaxin‐1, and is a constituent of the post‐synaptic density. Moreover, in vitro‐binding assays indicate that Nesca directly binds KIF5B, kinesin light‐chain and syntaxin‐1. In contrast, Nesca does not co‐immunoprecipitate with the kinesin motors KIF1B, KIF3A nor does it bind syntaxin‐4 or the synaptosome‐associated protein 25 kDa (SNAP‐25) in vitro. Nesca expression in neurons is highly punctuate, co‐stains with syntaxin‐1, and is found in fractions containing markers of early endosomes and Golgi suggesting that it is involved in vesicular transport. Collectively, these data suggest that Nesca functions as an adapter involved in neuronal vesicular transport including vesicles containing soluble N‐ethylmaleimide sensitive factor attachment protein receptors that are essential to exocytosis. Nesca is a novel adapter protein that is exclusively expressed in the nervous system. Until now, however, a functional role for Nesca has been unknown. Using cell biology, confocal microscopy and in vitro‐binding studies, we show that Nesca is a novel microtubule‐binding protein, that it binds the kinesin motor KIF5 and the synaptic membrane precursor protein syntaxin‐1. These studies suggest that Nesca serves a role, similar to syntabulin, in the anterograde transport of synaptic membrane precursor proteins essential to exocytosis.
Bibliography:	ArticleID:JNC7729 istex:A5C69175FE8F5438E72F3881320C20BA1B635C66 ark:/67375/WNG-RWD9W0Z3-7 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3042 1471-4159
DOI:	10.1111/j.1471-4159.2012.07729.x