Dynein binds and stimulates axonal motility of the endosome adaptor and NEEP21 family member, calcyon

Liang Shi, Nagendran Muthusamy, Deanna Smith, Clare Bergson

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The neuron-enriched, endosomal protein Calcyon (Caly) regulates endocytosis and vesicle sorting, and is important for synaptic plasticity and brain development. In the current investigation of Caly interacting proteins in brain, the microtubule retrograde motor subunit, cytoplasmic dynein 1 heavy chain (DYNC1H), and microtubule structural proteins, α and β tubulin, were identified as Caly associated proteins by MALDI-ToF/ToF. Direct interaction of the Caly-C terminus with dynein and tubulin was further confirmed in in vitro studies. In Cos-7 cells, mCherry-Caly moved along the microtubule network in organelles largely labeled by the late endosome marker Rab7. Expression of the dynein inhibitor CC1, produced striking alterations in Caly distribution, consistent with retrograde motors playing a prominent role in Caly localization and movement. In axons of cultured adult rat sensory neurons, Caly-positive organelles co-localized with dynein intermediate chain (DYNC1I1-isoform IC-1B) and the dynein regulator, lissencephaly 1 (LIS1), both of which co-precipitated from brain with the Caly C-terminus. Manipulation of dynein function in axons altered the motile properties of Caly indicating that Caly vesicles utilize the retrograde motor. Altogether, the current evidence for association with dynein motors raises the possibility that the endocytic and cargo sorting functions of Caly in neurons could be regulated by interaction with the microtubule transport system.

Original languageEnglish (US)
Pages (from-to)93-102
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Volume90
DOIs
StatePublished - Sep 2017

Keywords

  • AP-1
  • AP-2
  • AP-3
  • Adaptor protein
  • Brain
  • Clathrin
  • Endocytosis
  • Lysosome
  • Schizophrenia
  • Tubulin

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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