Sra-1 interacts with Kette and Wasp and is required for neuronal and bristle development in Drosophila.
Regulation of growth cone and cell motility involves the coordinated control of F-actin dynamics. An important regulator of F-actin formation is the Arp2/3 complex, which in turn is activated by Wasp and Wave. A complex comprising Kette/Nap1, Sra-1/Pir121/CYFIP, Abi and HSPC300 modulates the activity of Wave and Wasp. We present the characterization of Drosophila Sra-1 (specifically Rac1-associated protein 1). sra-1 and kette are spatially and temporally co-expressed, and both encoded proteins interact in vivo. During late embryonic and larval development, the Sra-1 protein is found in the neuropile. Outgrowing photoreceptor neurons express high levels of Sra-1 also in growth cones. Expression of double stranded sra-1 RNA in photoreceptor neurons leads to a stalling of axonal growth. Following knockdown of sra-1 function in motoneurons, we noted abnormal neuromuscular junctions similar to what we determined for hypomorphic kette mutations. Similar mutant phenotypes were induced after expression of membrane-bound Sra-1 that lacks the Kette-binding domain, suggesting that sra-1 function is mediated through kette. Furthermore, we could show that both proteins stabilize each other and directly control the regulation of the F-actin cytoskeleton in a Wasp-dependent manner.
Institut für Neurobiologie, Universität Münster, Badestrasse 9, Münster 48149, Germany.
Sven
S
Bogdan
Oliver
O
Grewe
Mareike
M
Strunk
Alexandra
A
Mertens
Christian
C
Klämbt
D000199:Actins / Q000096:biosynthesis; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001369:Axons / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004843:Epistasis, Genetic; D005124:Eye Abnormalities / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C484666:Sra-1 protein, Drosophila; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; C478569:hem protein, Drosophila