Universität zu Köln

Seifert, Wenke, Kuehnisch, Jirko, Maritzen, Tanja ORCID: 0000-0003-4993-0340, Lommatzsch, Stefanie, Hennies, Hans Christian, Bachmann, Sebastian, Horn, Denise and Haucke, Volker ORCID: 0000-0003-3119-6993 (2015). Cohen Syndrome-associated Protein COH1 Physically and Functionally Interacts with the Small GTPase RAB6 at the Golgi Complex and Directs Neurite Outgrowth. J. Biol. Chem., 290 (6). S. 3349 - 3359. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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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:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Seifert, Wenke UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuehnisch, Jirko UNSPECIFIED UNSPECIFIED UNSPECIFIED Maritzen, Tanja UNSPECIFIED orcid.org/0000-0003-4993-0340 UNSPECIFIED Lommatzsch, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Hennies, Hans Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Bachmann, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Horn, Denise UNSPECIFIED UNSPECIFIED UNSPECIFIED Haucke, Volker UNSPECIFIED orcid.org/0000-0003-3119-6993 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-412637
DOI:	10.1074/jbc.M114.608174
Journal or Publication Title:	J. Biol. Chem.
Volume:	290
Number:	6
Page Range:	S. 3349 - 3359
Date:	2015
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN CEREBRAL-CORTEX; MEMBRANE TRAFFICKING; MUTATIONAL SPECTRUM; GENE; TRANSPORT; NEURONS; HETEROGENEITY; GLYCOSYLATION; LOCALIZATION; HOMEOSTASIS Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41263