Research Group Intracellular MembraneTransport (Dr. Wenke Seifert)
Our research group focusses on two topics important for neuronal development, the Golgi complex in intracellular membrane transport, and the regulation of microtubule dynamics. We study these processes in the context of genetically-inherited microcephaly combined with intellectual disability by using cell biological approaches, molecular biology techniques, and protein biochemistry.
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Cohen syndrome
Intracellular membrane transport controls a wide spectrum of biological processes such as brain development and maintenance. Core determinants of regular brain function are neuronal differentiation and integration into an efficient network. Studying inherited neurological disorders may help to define molecular mechanisms underlying these processes.
Our team focusses on the autosomal recessive Cohen syndrome, which is mainly characterized by non-progressive intellectual disability in combination with postnatal microcephaly.
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 (Seifert et al, 2011). Moreover, we showed that association of VPS13B with the Golgi complex depends on RAB6 GTPase activity (Seifert et al, 2014)
Molecular machinery that is controlled by VPS13B
In general, our goal is to provide profound insights into the molecular machinery that is controlled by VPS13B to facilitate Golgi function, intracellular transport, and ultimately normal neuronal function. Our ongoing work focusses on Vps13b expression analyses, cortical development studies, and identification of other VPS13B interactors similar to the known yeast Vps13p network. Initial experiments demonstrate that depletion of VPS13B in primary neurons negatively interferes with neurite outgrowth, indicating a causal link between the integrity of the Golgi complex and axonal outgrowth (Seifert et al., 2014). Our work will provide the cell biological understanding of the molecular functions of VPS13B in the brain offering essential insights into the neuropathology of Cohen syndrome. At the same time, our results will contribute to the general comprehension how Golgi-associated transport processes impact terminal neuronal differentiation, integration and function.