Tethering Membrane Fusion: Common and Different Players in Myoblasts and at the Synapse

Abstract

DrosophilaMembrane fusion is essential for the communication of membrane-defined compartments, development of multicellular organisms and tissue homeostasis. Although membrane fusion has been studied extensively, still little is known about the molecular mechanisms. Especially the intercellular fusion of cells during development and tissue homeostasis is poorly understood. Somatic muscle formation in Drosophila depends on the intercellular fusion of myoblasts. In this process, myoblasts recognize each other and adhere, thereby triggering a protein machinery that leads to electron-dense plaques, vesicles and F-actin formation at apposing membranes. Two models of how local membrane stress is achieved to induce the merging of the myoblast membranes have been proposed: the electron-dense vesicles transport and release a fusogen and F-actin bends the plasma membrane. In this review, we highlight cell-adhesion molecules and intracellular proteins known to be involved in myoblast fusion. The cell-adhesion proteins also mediate the recognition and adhesion of other cell types, such as neurons that communicate with each other via special intercellular junctions, termed chemical synapses. At these synapses, neurotransmitters are released through the intracellular fusion of synaptic vesicles with the plasma membrane. As the targeting of electron-dense vesicles in myoblasts shares some similarities with the targeting of synaptic vesicle fusion, we compare molecules required for synaptic vesicle fusion to recently identified molecules involved in myoblast fusion.

Acting on identity: Myoblast fusion and the formation of the syncytial muscle fiber

“…For membrane fusion to proceed, however, N-cadherin needs to be removed from the fusion site (Hamp et al, 2016). Kette and Schizo/Loner, upstream regulators of Arp2/3-mediated actin rearrangements (see Actin rearrangement section below), are reported to facilitate removal of N-cadherin (Hamp et al, 2016, Dottermusch-Heidel et al, 2012, Onel et al, 2014). Notably, N-cadherin loss of function does not result in fusion defects in the Drosophila embryo (Charlton et al, 1997; Dottermusch-Heidel et al, 2012), suggesting potential redundant functions with other members of the cadherin family.…”

Expression of Hbs, Kirre, and Rst during Drosophila ovarian development

“…Investigation of IRM involvement in Drosophila gonadal development have so far been limited to their role in myoblast fusion of multinucleated smooth‐like muscle fibers that enclose the testis (Susic‐Jung et al, ; Kuckwa et al, ). In this developmental scenario, although all four genes appear to be required for muscle precursor fusion, their precise mode of action might not be identical to the one extensively characterized in both embryonic and adult somatic myogenesis (Gildor et al, ; Önel et al, ). Particularly rst and kirre seem to act agonistically, rather than redundantly during myotube generation in the testis (Kuckwa et al, ).…”

News in fusion

“…Alle bisherigen Untersuchungen weisen darauf hin, dass die Arp2/3‐basierte F‐Aktin‐Polymerisation mehrere Funktionen während der Myoblastenfusion übernimmt. Im Laufe der Jahre wurde gezeigt, dass die Bildung von verzweigtem F‐Aktin sowohl für die Verringerung des Membranabstandes zwischen fusionierenden Myoblasten als auch für die Bildung einer Fusionspore verantwortlich ist . Nach der Bildung einer Fusionspore weitet sich diese und die FCM wird in die FC integriert.…”

“…Nach der Bildung einer Fusionspore weitet sich diese und die FCM wird in die FC integriert. Dadurch bildet sich eine wachsende synzytiale Myotube, die mit weiteren FCMs fusioniert . Die Ursache für die verschiedenen Funktionen der F‐Aktin‐Polymerisation im Verlauf der Myoblastenfusion könnte am unterschiedlichen Zusammenspiel der Nukleations‐Promotions‐Faktoren Scar/WAVE und WASp liegen.…”