Characterization of the Cohen syndrome protein COH1 as a membrane-associated scaffold protein for intracellular transport processes in development and maintenance of neuronal cells
Final Report Abstract
Autosomal recessive Cohen syndrome is mainly characterized by non-progressive intellectual disability in combination with postnatal microcephaly. Cohen syndrome is caused by mutations in the VPS13B (COH1) gene. VPS13B encodes a pioneer protein of 3997 amino acids (450 kDa) length with partial sequence homology to yeast Vps13p. We established VPS13B (also known as COH1) as Golgi-associated protein influencing Golgi morphology and Golgi-associated membrane tubulation activity. Moreover, we showed that association of VPS13B with the Golgi complex depends on RAB6 activity. Our ongoing work focusses on Vps13b expression analyses, cortical development studies and identification of other VPS13B interactors similar to the known yeast Vps13p network. Our goal is to provide profound insights into the molecular machinery that is controlled by VPS13B to facilitate Golgi function and intracellular transport. Combined biochemical, genetic and cell biological approaches ensure the integration of our research to formulate a pathomechanistic model of Cohen syndrome. At the same time, our results will significantly contribute to the general comprehension of Golgi-associated transport processes for terminal neuronal differentiation and integration.
Publications
- The Cohen syndromeassociated protein COH1 is a novel, giant Golgi matrix protein required for Golgi integrity. Golgi Symposia 2013, Österreich
Wenke Seifert, Jirko Kühnisch, Tanja Maritzen, Stefanie Lommatzsch, Malte Zorn, Sebastian Bachmann, Denise Horn, Volker Haucke, Hans Christian Hennies
- Functional studies of the Cohen syndrome-associated protein VPS13B (COH1), Third joint symposium on neuroacanthocytosis and neurodegeneration with brain iron accumulation, Stresa, Italy 2014
Wenke Seifert, Jirko Kühnisch, Tanja Maritzen, Stefanie Lommatzsch, Hans Christian Hennies, Sebastian Bachmann, Denise Horn, Volker Haucke
- Interaction of the Cohen Syndrome-associated protein COH1 with RAB6 and RIC1/RGP1 emphasizes its role for Golgi function. GFH 2014, Italien
Wenke Seifert, Jirko Kühnisch, Tanja Maritzen, Stefanie Lommatzsch, Malte Zorn, Sebastian Bachmann, Denise Horn, Volker Haucke, Hans Christian Hennies
- 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 02/2015;290(6):3349-58
Wenke Seifert, Jirko Kühnisch, Tanja Maritzen, Stefanie Lommatzsch, Hans Christian Hennies, Sebastian Bachmann, Denise Horn, Volker Haucke
(See online at https://doi.org/10.1074/jbc.M114.608174) - The small GTPase RAB6 regulates localization of the Cohen syndrome-associated protein COH1 to the Golgi complex, 40th Congress of The Federation of European Biochemical Societies, Berlin, Germany, 2015
Stefanie Lommatzsch, Jirko Kühnisch, Tanja Maritzen, Sebastian Bachmann, Denise Horn, Volker Haucke, Wenke Seifert
- The small GTPase RAB6 regulates localization of the Cohen syndrome-associated protein COH1 to the Golgi complex. FEBS 2015, Berlin
Stefanie Lommatzsch, Jirko Kühnisch, Tanja Maritzen, Sebastian Bachmann, Denise Horn, Volker Haucke, Wenke Seifert
- Functional Studies of the Cohen Syndrome-associated Protein VPS13B (COH1), 9th International Meeting on Neuroacanthocytosis Syndromes, Dresden, Germany, 2018
Stefanie Lommatzsch, Malte Zorn, Jirko Kühnisch, Denise Horn, Volker Haucke, Wenke Seifert
- Charakterisierung des Cohen-Syndrom-assoziierten Proteins Coh1 während der Neurogenese im Cortex cerebri der Maus. FU Berlin 2019
Stefanie Lommatzsch
(See online at https://dx.doi.org/10.17169/refubium-1526) - Charakterisierung von Cohen-Syndrom-assoziierten missense-Varianten. Charité – Universitätsmedizin Berlin 2019
Malte Zorn
