Cytoplasmic dynein and its regulatory proteins in Golgi pathology in nervous system disorders

• Published in: Frontiers in neuroscience Vol. 9; p. 397
• Main Authors: Jaarsma, Dick, Hoogenraad, Casper C
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 26.10.2015; Frontiers Media S.A
• Subjects: Axonogenesis; Axons; Cell body; Cell cycle; Dendrites; Dynactin; Dynein; Golgi; Golgi cells; Lipids; lis1; Motor neuron diseases; Mutation; Nervous system; Neurodegenerative diseases; Neurodegenerative disorders; Neurons; Neuropathy; Proteins; Psychiatry; Regulation; Regulatory proteins; transport; Netherlands; dynein; Golgin 160; Golgi; transport; dynactin; neurodegenerative disorders; BICD2; Lis1
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2015.00397

The Golgi apparatus is a dynamic organelle involved in processing and sorting of lipids and proteins. In neurons, the Golgi apparatus is important for the development of axons and dendrites and maintenance of their highly complex polarized morphology. The motor protein complex cytoplasmic dynein has an important role in Golgi apparatus positioning and function. Together, with dynactin and other regulatory factors it drives microtubule minus-end directed motility of Golgi membranes. Inhibition of dynein results in fragmentation and dispersion of the Golgi ribbon in the neuronal cell body, resembling the Golgi abnormalities observed in some neurodegenerative disorders, in particular motor neuron diseases. Mutations in dynein and its regulatory factors, including the dynactin subunit p150Glued, BICD2 and Lis-1, are associated with several human nervous system disorders, including cortical malformation and motor neuropathy. Here we review the role of dynein and its regulatory factors in Golgi function and positioning, and the potential role of dynein malfunction in causing Golgi apparatus abnormalities in nervous system disorders.