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The MAP1B-LC1/UBE2L3 complex catalyzes degradation of cell surface CaV2.2 channels

María A Gandini1, Alejandro Sandoval, Gerald W Zamponi

  • 1a Department of Cell Biology; Center for Research and Advanced Studies of the National Polytechnic Institute ; Mexico City , Mexico.

Channels (Austin, Tex.)
|December 9, 2014
PubMed

Insights

Microtubule-associated protein B light chain 1 (MAP1B-LC1) regulates neuronal calcium channel (CaV2.2) expression via ubiquitination and internalization. This pathway may be conserved across N-type and P/Q-type channels.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Neuronal N-type calcium channels (CaV2.2) play critical roles in synaptic function.
  • Regulation of CaV2.2 channel expression is crucial for neuronal excitability.
  • Ubiquitination is a key post-translational modification controlling protein degradation and localization.

Purpose of the Study:

  • To elucidate the mechanism by which MAP1B-LC1 regulates CaV2.2 channel expression.
  • To investigate the role of ubiquitination and protein trafficking in this regulation.
  • To explore the potential conservation of this regulatory mechanism in other calcium channel types.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Ubiquitination assays to assess channel modification.
  • Confocal microscopy to visualize channel localization.
  • Pharmacological inhibition of the ubiquitin-proteasome system and endocytosis pathways.

Main Results:

  • MAP1B-LC1 interacts with both CaV2.2e37a and CaV2.2e37b variants.
  • MAP1B-LC1 promotes ubiquitination and degradation of CaV2.2 channels.
  • MAP1B-LC1-mediated CaV2.2 channel regulation involves clathrin- and dynamin-dependent internalization.
  • Inhibition of the ubiquitin-proteasome pathway prevents MAP1B-LC1-induced degradation.

Conclusions:

  • MAP1B-LC1 is a novel regulator of CaV2.2 channel expression through ubiquitination and endocytosis.
  • This mechanism involves channel internalization via a clathrin- and dynamin-dependent pathway.
  • The findings suggest a conserved regulatory mechanism for N-type and P/Q-type calcium channels.
Keywords:
BFA, brefeldin ABrefeldin ADRG, dorsal root ganglionDynasoreHVA, high-voltage-activatedLC1MAP1BMAP1B-LC1, Microtubule-associated protein 1B light chainN-type channelsUBE2L3UBE2L3, Ubiquitin-conjugating enzyme E2 L3UPS, Ubiquitin proteasome systemtrafficking

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