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

• Type of Material: Article
• Authors: Cortnie Hartwig, Emory University; William J. Monis, University of Massachusetts; Xun Chen, University of Southern California; Dion K. Dickman, University of Southern California; Gregory J. Pazour, University of Massachusetts; Victor Faundez, Emory University
• Language: English
• Date: 2018-03-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/dneu.22542
• Title of Journal or Parent Work: Developmental Neurobiology
• ISSN: 1932-8451
• Volume: 78
• Issue: 3
• Start Page: 311
• End Page: 330
• Grant/Funding Information: This work was supported by grants from the Emory Catalyst Award and National Institutes of Health to V.F. (NS42599), DKD (NS091546), and GJP (GM060992 and DK103632).
• Keywords: BORCS7; BLOC-1; schizophrenia; Developmental Biology; Neurosciences & Neurology; DYSBINDIN-1 MESSENGER-RNA; cilium; 22Q11.2 DELETION SYNDROME; SCHIZOPHRENIA SUSCEPTIBILITY GENE; MEMBRANE-FUSION; DEVELOPING CEREBRAL-CORTEX; dysbindin; CLATHRIN-MEDIATED ENDOCYTOSIS; HERMANSKY-PUDLAK-SYNDROME; Neurosciences; Science & Technology; EXOME SEQUENCING REVEALS; LYSOSOME-RELATED ORGANELLES; Life Sciences & Biomedicine; DORSOLATERAL PREFRONTAL CORTEX
• Research Categories: Biology, Neuroscience; Biology, Molecular; Biology, Cell

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.