Molecular Mechanisms of Centrosome and Cytoskeleton Anchorage at the Nuclear Envelope

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2010 Oct 6

PMID 20922455

Citations 49

Authors

Maria Schneider

Wenshu Lu

Sascha Neumann

Andreas Brachner

Josef Gotzmann

Angelika A Noegel

Iakowos Karakesisoglou

Affiliations

Soon will be listed here.

Abstract

Cell polarization is a fundamental process underpinning organismal development, and tissue homeostasis, which requires an orchestrated interplay of nuclear, cytoskeletal, and centrosomal structures. The underlying molecular mechanisms, however, still remain elusive. Here we report that kinesin-1/nesprin-2/SUN-domain macromolecular assemblies, spanning the entire nuclear envelope (NE), function in cell polarization by anchoring cytoskeletal structures to the nuclear lamina. Nesprin-2 forms complexes with the kinesin-1 motor protein apparatus by associating with and recruiting kinesin light chain 1 (KLC1) to the outer nuclear membrane. Similar to nesprin-2, KLC1 requires lamin A/C for proper NE localization. The depletion of nesprin-2 or KLC1, or the uncoupling of nesprin-2/SUN-domain protein associations impairs cell polarization during wounding and dislodges the centrosome from the NE. In addition nesprin-2 loss has profound effects on KLC1 levels, the cytoskeleton, and Golgi apparatus organization. Collectively these data show that NE-associated proteins are pivotal determinants of cell architecture and polarization.

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