Nesprins, nuclear dystrophin-like integrators of the cyto- and nucleoskeleton

• Applicant: Dr. Iakowos Karakesisoglou
• Subject Area: Cell Biology
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 27993483

Nesprins are giant vertebrate dystrophin like proteins (>800 kDa) of the nuclear envelope. Whereas their N-terminus contains an ¿-actinin type actin binding domain enabling an association with the actin cytoskeleton, their C-terminus contains a single transmembrane domain which targets the protein specifically to the nuclear membrane. Genetic studies in C. elegans implicate Nesprins in nuclear migration and nuclear anchorage; the mechanism however by which such functions are established remains elusive. Recent evidence in our laboratory indicates that Nesprins associate directly with p150-Glued and kinesin light chain 1. The scopes of this proposal are to unravel the molecular details of Nesprin mediated interactions with microtubule motor proteins and the cytoskeleton and to study their functional importance in various aspects of nuclear biology. In order to accomplish this we will use a combination of biochemical, cell biological and genetic approaches. Elucidating the function of Nesprins and their associations may help to delineate and disentangle fundamental cell biological processes, providing thus a basis towards a better understanding of laminopathic human diseases.

• DFG Programme: Research Grants