RRC ID 59038
著者 Beyenbach KW, Schöne F, Breitsprecher LF, Tiburcy F, Furuse M, Izumi Y, Meyer H, Jonusaite S, Rodan AR, Paululat A.
タイトル The septate junction protein Tetraspanin 2A is critical to the structure and function of Malpighian tubules in Drosophila melanogaster.
ジャーナル Am J Physiol Cell Physiol
Abstract Tetraspanin-2A (Tsp2A) is an integral membrane protein of smooth septate junctions in Drosophila melanogaster. To elucidate its structural and functional roles in Malpighian tubules, we used the c42-GAL4/UAS system to selectively knock down Tsp2A in principal cells of the tubule. Tsp2A localizes to smooth septate junctions (sSJ) in Malpighian tubules in a complex shared with partner proteins Snakeskin (Ssk), Mesh, and Discs large (Dlg). Knockdown of Tsp2A led to the intracellular retention of Tsp2A, Ssk, Mesh, and Dlg, gaps and widening spaces in remaining sSJ, and tumorous and cystic tubules. Elevated protein levels together with diminished V-type H+-ATPase activity in Tsp2A knockdown tubules are consistent with cell proliferation and reduced transport activity. Indeed, Malpighian tubules isolated from Tsp2A knockdown flies failed to secrete fluid in vitro. The absence of significant transepithelial voltages and resistances manifests an extremely leaky epithelium that allows secreted solutes and water to leak back to the peritubular side. The tubular failure to excrete fluid leads to extracellular volume expansion in the fly and to death within the first week of adult life. Expression of the c42-GAL4 driver begins in Malpighian tubules in the late embryo and progresses upstream to distal tubules in third instar larvae, which can explain why larvae survive Tsp2A knockdown and adults do not. Uncontrolled cell proliferation upon Tsp2A knockdown confirms the role of Tsp2A as tumor suppressor in addition to its role in sSJ structure and transepithelial transport.
巻・号 318(6)
ページ C1107-C1122
公開日 2020-6-1
DOI 10.1152/ajpcell.00061.2020
PMID 32267718
PMC PMC7311739
MeSH Animals Animals, Genetically Modified Cell Proliferation Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / embryology Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Drosophila melanogaster / ultrastructure Electric Impedance Epithelial Cells / metabolism* Epithelial Cells / ultrastructure Gene Expression Regulation, Developmental Gene Knockdown Techniques Larva / genetics Larva / metabolism Larva / ultrastructure Malpighian Tubules / embryology Malpighian Tubules / metabolism* Malpighian Tubules / ultrastructure Secretory Pathway Signal Transduction Tetraspanins / genetics Tetraspanins / metabolism* Tight Junctions / genetics Tight Junctions / metabolism* Tight Junctions / ultrastructure Vacuolar Proton-Translocating ATPases / genetics Vacuolar Proton-Translocating ATPases / metabolism
IF 3.485
引用数 1
リソース情報
ショウジョウバエ 11415R-2