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Mol Biol Cell. 2010 Sep 15;21(18):3162-70. doi: 10.1091/mbc.E09-12-1058. Epub 2010 Jul 28.

Expression of actin-interacting protein 1 suppresses impaired chemotaxis of Dictyostelium cells lacking the Na+-H+ exchanger NHE1.

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  • 1Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.


Increased intracellular pH is an evolutionarily conserved signal necessary for directed cell migration. We reported previously that in Dictyostelium cells lacking H(+) efflux by a Na(+)-H(+) exchanger (NHE; Ddnhe1(-)), chemotaxis is impaired and the assembly of filamentous actin (F-actin) is attenuated. We now describe a modifier screen that reveals the C-terminal fragment of actin-interacting protein 1 (Aip1) enhances the chemotaxis defect of Ddnhe1(-) cells but has no effect in wild-type Ax2 cells. However, expression of full-length Aip1 mostly suppresses chemotaxis defects of Ddnhe1(-) cells and restores F-actin assembly. Aip1 functions to promote cofilin-dependent actin remodeling, and we found that although full-length Aip1 binds cofilin and F-actin, the C-terminal fragment binds cofilin but not F-actin. Because pH-dependent cofilin activity is attenuated in mammalian cells lacking H(+) efflux by NHE1, our current data suggest that full-length Aip1 facilitates F-actin assembly when cofilin activity is limited. We predict the C-terminus of Aip1 enhances defective chemotaxis of Ddnhe1(-) cells by sequestering the limited amount of active cofilin without promoting F-actin assembly. Our findings indicate a cooperative role of Aip1 and cofilin in pH-dependent cell migration, and they suggest defective chemotaxis in Ddnhe1(-) cells is determined primarily by loss of cofilin-dependent actin dynamics.

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