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Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth

Seifert, W., Kühnisch, J., Maritzen, T., Lommatzsch, S., Hennies, Hans C., Bachmann, S., Horn, D. and Haucke, V. (2015) Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth. Journal of Biological Chemistry, 290 (6). pp. 3349-3358. ISSN 0021-9258

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Abstract

Postnatal microcephaly, intellectual disability, and progressive retinal dystrophy are major features of autosomal recessive Cohen syndrome, which is caused by mutations in the gene COH1 (VPS13B). We have recently identified COH1 as a Golgi-enriched scaffold protein that contributes to the structural maintenance and function of the Golgi complex. Here, we show that association of COH1 with the Golgi complex depends on the small GTPase RAB6. RNAi-mediated knockdown of RAB6A/A' prevents the localization of COH1 to the Golgi complex. Expression of the constitutively inactive RAB6_T27N mutant led to an increased solubilization of COH1 from lipid membrane preparations. Co-IP experiments confirmed the physical interaction of COH1 with RAB6 that preferentially occurred with the constitutively active RAB6_Q72L mutants. Depletion of COH1 in primary neurons negatively interfered with neurite outgrowth, indicating a causal link between the integrity of the Golgi complex and axonal outgrowth. We conclude that COH1 is a RAB6 effector protein and that reduced brain size in Cohen syndrome patients likely results from impaired COH1 function at the Golgi complex, causing decreased neuritogenesis.

Item Type: Article
Additional Information: Unmapped bibliographic data: ST - Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth [Field not mapped to EPrints] C2 - PMC4319006 [Field not mapped to EPrints] AD - From the Institute of Vegetative Anatomy, Charite - Universitatsmedizin Berlin, 10115 Berlin, Germany, wenke.seifert@charite.de. [Field not mapped to EPrints] AN - 25492866 [Field not mapped to EPrints]
Uncontrolled Keywords: Animals
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Schools: School of Applied Sciences
Depositing User: Hans Hennies
Date Deposited: 06 Jul 2016 11:00
Last Modified: 29 Jul 2016 13:01
URI: http://eprints.hud.ac.uk/id/eprint/28756

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