Nesprin 4 Is an Outer Nuclear Membrane Protein That Can Induce Kinesin-Mediated Cell Polarization
Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization Kyle J. Rouxa,1,2, Melissa L. Crispa,1, Qian Liua, Daein Kima, Serguei Kozlovb, Colin L. Stewartc, and Brian Burkea,2 aDepartment of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610; cInstitute of Medical Biology, Immunos, 8A Biomedical Grove, Republic of Singapore 138648; and bCenter for Advanced Preclinical Research and Mouse Cancer Genetics Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702 Edited by Don W. Cleveland, University of California at San Diego, La Jolla, CA, and approved December 19, 2008 (received for review September 2, 2008) Nucleocytoplasmic coupling is mediated by outer nuclear mem- by a short luminal sequence. Localization of ONM KASH brane (ONM) nesprin proteins and inner nuclear membrane Sun proteins depends on tethering by SUN domain proteins of the proteins. Interactions spanning the perinuclear space create ne- INM (18). This tethering, involving interactions spanning the sprin–Sun complexes connecting the cytoskeleton to nuclear com- PNS, was originally suggested based on findings that localization ponents. A search for proteins displaying a conserved C-terminal of Anc-1 depends on an INM protein, Unc-84 (19, 20), a sequence present in nesprins 1–3 identified nesprin 4 (Nesp4), a prototype member of the SUN family. new member of this family. Nesp4 is a kinesin-1-binding protein Three mammalian nesprin genes are known [nesprins 1–3 (7)]. that displays Sun-dependent localization to the ONM. Expression For nesprins 1 and 2, the primary transcripts encode a plethora of Nesp4 is associated with dramatic changes in cellular organiza- of alternatively-spliced isoforms (9).
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