RGD Reference Report - The role of MAP1A light chain 2 in synaptic surface retention of Cav2.2 channels in hippocampal neurons. - Rat Genome Database

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The role of MAP1A light chain 2 in synaptic surface retention of Cav2.2 channels in hippocampal neurons.

Authors: Leenders, A G Miriam  Lin, Lin  Huang, Li-Dong  Gerwin, Claudia  Lu, Pei-Hua  Sheng, Zu-Hang 
Citation: Leenders AG, etal., J Neurosci. 2008 Oct 29;28(44):11333-46. doi: 10.1523/JNEUROSCI.3078-08.2008.
RGD ID: 405650353
Pubmed: PMID:18971475   (View Abstract at PubMed)
PMCID: PMC2596948   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3078-08.2008   (Journal Full-text)

Ca(v)2.2 channels are localized at nerve terminals where they play a critical role in neurotransmission. However, the determinant that controls surface retention of these channels has not been identified. Here, we report that presynaptic surface localization of Ca(v)2.2 is mediated through its interaction with light chain 2 (LC2) of microtubule-associated protein MAP1A. Deletion of a 23-residue binding domain within the Ca(v)2.2 C terminus resulted in reduced synaptic distribution of the mutant channels. Using an antibody generated against an extracellular epitope of Ca(v)2.2, we demonstrate that interfering the interaction with LC2 reduced surface expression of endogenous Ca(v)2.2 at presynaptic boutons. In addition, the disruption of LC2-Ca(v)2.2 coupling reduced Ca(2+)-influx into nerve terminals through Ca(v)2.2 and impaired activity-dependent FM4-64 uptake. The treatments of neurons with Latrunculin A to disrupt actin filaments resulted in reduced density of surface Ca(v)2.2-positive boutons. Furthermore, LC2NT, a LC2 truncated mutant lacking the actin-binding domain, could not rescue Ca(v)2.2 surface expression after suppressing LC2 expression with RNAi. Because actin filaments are major cytomatric components at the presynaptic boutons, these observations suggest a mechanism by which LC2 provides anchoring of surface Ca(v)2.2 to the actin cytoskeleton, thus contributing to presynaptic function.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glutamatergic synapse is_active_inIDA 405650353PMID:18971475SynGO 
glutamatergic synapse is_active_inIEP 405650353PMID:18971475SynGO 
postsynaptic density is_active_inIDA 405650353PMID:18971475SynGO 
postsynaptic density is_active_inIEP 405650353PMID:18971475SynGO 
presynaptic active zone is_active_inIDA 405650353PMID:18971475SynGO 
presynaptic active zone is_active_inIEP 405650353PMID:18971475SynGO 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
structural constituent of presynapse enablesIDA 405650353PMID:18971475SynGO 
structural constituent of presynapse enablesIEP 405650353PMID:18971475SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Map1a  (microtubule-associated protein 1A)


Additional Information