Document Detail


Microtubule plus-end tracking protein CLASP2 regulates neuronal polarity and synaptic function.
MedLine Citation:
PMID:  23035100     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Microtubule organization and dynamics are essential during axon and dendrite formation and maintenance in neurons. However, little is known about the regulation of microtubule dynamics during synaptic development and function in mammalian neurons. Here, we present evidence that the microtubule plus-end tracking protein CLASP2 (cytoplasmic linker associated protein 2) is a key regulator of axon and dendrite outgrowth that leads to functional alterations in synaptic activity and formation. We found that CLASP2 protein levels steadily increase throughout neuronal development in the mouse brain and are specifically enriched at the growth cones of extending neurites. The short-hairpin RNA-mediated knockdown of CLASP2 in primary mouse neurons decreased axon and dendritic length, whereas overexpression of human CLASP2 caused the formation of multiple axons, enhanced dendritic branching, and Golgi condensation, implicating CLASP2 in neuronal morphogenesis. In addition, the CLASP2-induced morphological changes led to significant functional alterations in synaptic transmission. CLASP2 overexpression produced a large increase in spontaneous miniature event frequency that was specific to excitatory neurotransmitter release. The changes in presynaptic activity produced by CLASP2 overexpression were accompanied by increases in presynaptic terminal circumference, total synapse number, and a selective increase in presynaptic proteins that are involved in neurotransmitter release. Also, we found a smaller increase in miniature event amplitude that was accompanied by an increase in postsynaptic surface expression of GluA1 receptor localization. Together, these results provide evidence for involvement of the microtubule plus-end tracking protein CLASP2 in cytoskeleton-related mechanisms underlying neuronal polarity and interplay between microtubule stabilization and synapse formation and activity.
Authors:
Uwe Beffert; Gregory M Dillon; Josefa M Sullivan; Christine E Stuart; James P Gilbert; John A Kambouris; Angela Ho
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  32     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-04     Completed Date:  2013-01-17     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13906-16     Citation Subset:  IM    
Affiliation:
Department of Biology, Boston University, Boston, Massachusetts 02215, USA. ub1@bu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Axons / ultrastructure
Cell Polarity / physiology*
Cells, Cultured / ultrastructure
Cytoskeleton / physiology*,  ultrastructure
Dendrites / ultrastructure
Female
Golgi Apparatus / ultrastructure
Growth Cones / ultrastructure
Humans
Male
Mice
Microtubule-Associated Proteins / antagonists & inhibitors,  genetics,  physiology*
Microtubules / physiology*
Morphogenesis / physiology
Nerve Tissue Proteins / physiology*
Neurogenesis / physiology
Neurons / ultrastructure*
Neurotransmitter Agents / secretion
Phosphatidylinositol 3-Kinases / physiology
Presynaptic Terminals / physiology
RNA Interference
RNA, Small Interfering / pharmacology
Recombinant Fusion Proteins / physiology
Synaptic Transmission / physiology*
Grant Support
ID/Acronym/Agency:
K01 AG027311/AG/NIA NIH HHS; K01 AG027311/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/CLASP2 protein, human; 0/CLASP2 protein, mouse; 0/Microtubule-Associated Proteins; 0/Nerve Tissue Proteins; 0/Neurotransmitter Agents; 0/RNA, Small Interfering; 0/Recombinant Fusion Proteins; EC 2.7.1.-/Phosphatidylinositol 3-Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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