Membrane wounding triggers ATP release and dysferlin-mediated intercellular calcium signaling.
Dysferlin is a Ca(2+)-binding protein found in many different cell types. It is required for membrane wound repair in muscle, but it is not known whether it has the same function in other cells. Here we report the activation of an intercellular signaling pathway in sea urchin embryos by membrane wounding that evokes Ca(2+) spikes in neighboring cells. This pathway was mimicked by ATP application, and inhibited by apyrase, cadmium, and omega-agatoxin-IVA. Microinjection of dysferlin antisense phosphorodiamidate morpholino oligonucleotides blocked this pathway, whereas control morpholinos did not. Co-injection of mRNA encoding human dysferlin with the inhibitory morpholino rescued signaling activity. We conclude that in sea urchin embryos dysferlin mediates Ca(2+)-triggered intercellular signaling in response to membrane wounding.
Covian-Nares
J Fernando
JF
Laboratory of Molecular Physiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
Koushik
Srinagesh V
SV
Puhl
Henry L
HL
Vogel
Steven S
SS
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D000073939:Dysferlin; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D036641:Microscopy, Fluorescence, Multiphoton; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D012617:Sea Urchins; D014945:Wound Healing / Q000235:genetics
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D016376:Oligonucleotides, Antisense; D002104:Cadmium; D000255:Adenosine Triphosphate; D001081:Apyrase