Short Stop provides an essential link between F-actin and microtubules during axon extension.
Coordination of F-actin and microtubule dynamics is important for cellular motility and morphogenesis, but little is known about underlying mechanisms. short stop (shot) encodes an evolutionarily conserved, neuronally expressed family of rod-like proteins required for sensory and motor axon extension in Drosophila melanogaster. We identify Shot isoforms that contain N-terminal F-actin and C-terminal microtubule-binding domains, and that crosslink F-actin and microtubules in cultured cells. The F-actin- and microtubule-binding domains of Shot are required in the same molecule for axon extension, though the length of the connecting rod domain can be dramatically reduced without affecting activity. Shot therefore functions as a cytoskeletal crosslinker in axon extension, rather than mediating independent interactions with F-actin and microtubules. A Ca(2+)-binding motif located adjacent to the microtubule-binding domain is also required for axon extension, suggesting that intracellular Ca(2+) release may regulate Shot activity. These results suggest that Shot coordinates regulated interactions between F-actin and microtubules that are crucial for neuronal morphogenesis.
Lee
Seungbok
S
Department of Cell Biology and Center for Molecular Neuroscience, C-2210 Medical Center North,Vanderbilt University Medical Center, Nashville, TN 37232-0295, USA.
Kolodziej
Peter A
PA
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000235:genetics; D002454:Cell Differentiation; D017124:Conserved Sequence; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D019143:Evolution, Molecular; D008840:Microfilament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology*; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism
D000199:Actins; D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D014404:Tubulin; C450828:shot protein, Drosophila