Expression of actin-interacting protein 1 suppresses impaired chemotaxis of Dictyostelium cells lacking the Na+-H+ exchanger NHE1.
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.
Choi
Chang-Hoon
CH
Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
Patel
Hitesh
H
Barber
Diane L
DL
D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D016764:Cell Polarity; D002633:Chemotaxis / Q000502:physiology*; D004023:Dictyostelium / Q000166:cytology / Q000502:physiology*; D055785:Gene Knockdown Techniques; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
D051339:Actin Depolymerizing Factors; D000199:Actins; D008840:Microfilament Proteins; D017923:Sodium-Hydrogen Exchangers; C115237:actin interacting protein 1