Neurodevelopmental disease mechanisms, primary cilia, and endosomes converge on the BLOC-1 and BORC complexes

Dev Neurobiol. 2018 Mar;78(3):311-330. doi: 10.1002/dneu.22542. Epub 2017 Oct 13.

Abstract

The biogenesis of lysosome-related organelles complex-1 (BLOC-1) and the bloc-one-related complex (BORC) are the cytosolic protein complexes required for specialized membrane protein traffic along the endocytic route and the spatial distribution of endosome-derived compartments, respectively. BLOC-1 and BORC complex subunits and components of their interactomes have been associated with the risk and/or pathomechanisms of neurodevelopmental disorders. Thus, cellular processes requiring BLOC-1 and BORC interactomes have the potential to offer novel insight into mechanisms underlying behavioral defects. We focus on interactions between BLOC-1 or BORC subunits with the actin and microtubule cytoskeleton, membrane tethers, and SNAREs. These interactions highlight requirements for BLOC-1 and BORC in membrane movement by motors, control of actin polymerization, and targeting of membrane proteins to specialized cellular domains such as the nerve terminal and the primary cilium. We propose that the endosome-primary cilia pathway is an underappreciated hub in the genesis and mechanisms of neurodevelopmental disorders. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 311-330, 2018.

Keywords: BLOC-1; BORCS7; cilium; dysbindin; schizophrenia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cilia / metabolism*
  • Endosomes / metabolism*
  • Humans
  • Nerve Tissue Proteins / metabolism*
  • Neurodevelopmental Disorders / metabolism*

Substances

  • Nerve Tissue Proteins