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Characterizing the Composition of Molecular Motors on Moving Axonal Cargo Using "Cargo Mapping" Analysis
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Characterizing the Composition of Molecular Motors on Moving Axonal Cargo Using "Cargo Mapping" Analysis

Published on: October 30, 2014

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The MYO6 interactome: selective motor-cargo complexes for diverse cellular processes

Janeska J de Jonge1, Christopher Batters1, Thomas O'Loughlin1

  • 1Cambridge Institute for Medical Research, University of Cambridge, UK.

FEBS Letters
|June 18, 2019
PubMed

Insights

Myosin VI (MYO6) is a unique motor protein crucial for cellular processes. Its C-terminal tail regulates cargo binding, motor activity, and cytoskeletal dynamics, impacting various human diseases.

Area of Science:

  • Cell Biology
  • Molecular Motors
  • Cytoskeletal Dynamics

Background:

  • Myosins are actin-based motor proteins essential for intracellular transport.
  • Myosin VI (MYO6) is unique, moving cargo towards the minus ends of actin filaments.
  • MYO6 dysfunction is linked to human pathologies like deafness, cancer, and neurodegenerative diseases.

Purpose of the Study:

  • To investigate the broader MYO6 interactome and its role in cytoskeletal regulation.
  • To understand how adaptor binding influences MYO6 conformation, dimerization, and motor activity.
  • To elucidate the function of the MYO6 C-terminal tail domain.

Main Methods:

  • Functional proteomics to identify MYO6 interacting proteins and complexes.
  • Analysis of MYO6 binding partners and their roles in the endocytic pathway.
  • Biochemical and biophysical studies on the C-terminal tail domain's function.

Main Results:

  • Identified large, functionally distinct multi-protein complexes within the MYO6 interactome.
  • Demonstrated that adaptor-binding controls MYO6's inactive folded conformation and dimerization.
  • Confirmed the C-terminal tail domain mediates cargo recognition, motor activity modulation, and cytoskeletal track regulation.

Conclusions:

  • MYO6 plays a critical role in regulating the actin and septin cytoskeleton through interactions with diverse protein complexes.
  • Adaptor interactions are key regulators of MYO6 conformation and activity.
  • The C-terminal tail domain is a multifunctional region critical for MYO6's cellular roles.
Keywords:
BioIDactinautophagycargo-bindingendocytosismyosin

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