WASP and SCAR have distinct roles in activating the Arp2/3 complex during myoblast fusion.
Myoblast fusion takes place in two steps in mammals and in Drosophila. First, founder cells (FCs) and fusion-competent myoblasts (FCMs) fuse to form a trinucleated precursor, which then recruits further FCMs. This process depends on the formation of the fusion-restricted myogenic-adhesive structure (FuRMAS), which contains filamentous actin (F-actin) plugs at the sites of cell contact. Fusion relies on the HEM2 (NAP1) homolog Kette, as well as Blow and WASP, a member of the Wiskott-Aldrich-syndrome protein family. Here, we show the identification and characterization of schwächling--a new Arp3-null allele. Ultrastructural analyses demonstrate that Arp3 schwächling mutants can form a fusion pore, but fail to integrate the fusing FCM. Double-mutant experiments revealed that fusion is blocked completely in Arp3 and wasp double mutants, suggesting the involvement of a further F-actin regulator. Indeed, double-mutant analyses with scar/WAVE and with the WASP-interacting partner vrp1 (sltr, wip)/WIP show that the F-actin regulator scar also controls F-actin formation during myoblast fusion. Furthermore, the synergistic phenotype observed in Arp3 wasp and in scar vrp1 double mutants suggests that WASP and SCAR have distinct roles in controlling F-actin formation. From these findings we derived a new model for actin regulation during myoblast fusion.
Berger
Susanne
S
Fachbereich Biologie, Entwicklungsbiologie, Philipps-Universität Marburg, Karl-von-Frisch Str. 8, D-35043 Marburg, Germany.
Schäfer
Gritt
G
Kesper
Dörthe A
DA
Holz
Anne
A
Eriksson
Therese
T
Palmer
Ruth H
RH
Beck
Lothar
L
Klämbt
Christian
C
Renkawitz-Pohl
Renate
R
Onel
Susanne-Filiz
SF
D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D008854:Microscopy, Electron; D016133:Polymerase Chain Reaction; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000502:physiology*
D051376:Actin-Related Protein 2-3 Complex; D017931:DNA Primers; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C449671:SCAR protein, Drosophila; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein