The Nucleo-cytoplasmic Actin-binding Protein CapG Lacks a Nuclear Export Sequence Present in Structurally Related Proteins

Katrien Van Impe, Veerle De Corte, Ludwig Eichinger, Erik Bruyneel, Marc Mareel, Joël Vandekerckhove, Jan Gettemans
2003 Journal of Biological Chemistry  
Despite thorough structure-function analyses, it remains unclear how CapG, a ubiquitous F-actin barbed end capping protein that controls actin microfilament turnover in cells, is able to reside in the nucleus and cytoplasm, whereas structurally related actin-binding proteins are predominantly cytoplasmic. Here we report the molecular basis for the different subcellular localization of CapG, severin, and fragminP. Green fluorescent protein-tagged fragminP and severin accumulate in the nucleus
more » ... n treatment of transfected cells with the CRM1 inhibitor leptomycin B. We identified a nuclear export sequence in severin and fragminP, which is absent in CapG. Deletion of amino acids Met 1 -Leu 27 resulted in nuclear accumulation of severin and fragminP. Tagging this sequence to CapG triggered nuclear export, whereas mutation of single leucine residues (Leu 17 , Leu 21 , and Leu 27 ) in the export sequence inhibited nuclear export. Based on these findings, a nuclear export signal was identified in myopodin, a muscle-specific actin-binding protein, and the Bloom syndrome protein, a RecQ-like helicase. Deletion of the myopodin nuclear export sequence blocked invasion into collagen type I of C2C12 cells transiently overexpressing myopodin. Our findings explain regulated subcellular targeting of distinct classes of actin-binding proteins.
doi:10.1074/jbc.m209946200 pmid:12637565 fatcat:pienspidzrbexdyxxybhg2qthm