M6 Membrane Protein Plays an Essential Role in Drosophila Oogenesis

Abstract

We had previously shown that the transmembrane glycoprotein M6a, a member of the proteolipid protein (PLP) family, regulates neurite/filopodium outgrowth, hence, M6a might be involved in neuronal remodeling and differentiation. In this work we focused on M6, the only PLP family member present in Drosophila, and ortholog to M6a. Unexpectedly, we found that decreased expression of M6 leads to female sterility. M6 is expressed in the membrane of the follicular epithelium in ovarioles throughout oogenesis. Phenotypes triggered by M6 downregulation in hypomorphic mutants included egg collapse and egg permeability, thus suggesting M6 involvement in eggshell biosynthesis. In addition, RNAi-mediated M6 knockdown targeted specifically to follicle cells induced an arrest of egg chamber development, revealing that M6 is essential in oogenesis. Interestingly, M6-associated phenotypes evidenced abnormal changes of the follicle cell shape and disrupted follicular epithelium in mid- and late-stage egg chambers. Therefore, we propose that M6 plays a role in follicular epithelium maintenance involving membrane cell remodeling during oogenesis in Drosophila.

A role for the membrane protein M6 in the Drosophila visual system

“…Therefore, M6 might play a dual role in cell remodeling in the visual system (present study) and epithelia [20]. …”

“…A w 1118 stock was used as the control. Potential M6 mutant stocks y 1 w 67c23 ; P{EPgy2}M6 EY07032 w 1118 ; P{GT1}M6 BG00390 and w 1118 ; Mi{ET1}M6 MB02608 / TM3, Sb 1 Ser 1 were obtained from the Bloomington Stock Center [21] and were renamed M6 01 M6 02 and M6 03 , respectively [20]. The CA06602 stock ( M6 GFP ) was obtained from the GFP Protein Trap Database at the Carnegie Institution [22].…”

“…The M6 01 M6 02 and M6 GFP strains were backcrossed several generations to w 1118 to minimize background effects. The original P-element (EY07032) from M6 01 was removed with the transposase (Δ2–3) and the reverted P-excised allele was kept as M6 Δ 01 -rev (for details see [20]).…”

Interplay between Anakonda, Gliotactin and M6 for tricellular junction assembly and anchoring of septate junctions inDrosophilaepithelium

“…M6 [30,31] localizes at tSJ at steady state in pupal notum. M6::GFP first appears in the form of a dispersed signal around 4-5 min after anaphase onset between the two daughter cells at and below midbody level ( Figure S1).…”

The transmembrane proteins M6 and Anakonda cooperate to initiate tricellular junction assembly in epithelia ofDrosophila

“…In Drosophila the transmembrane proteins Anakonda (Aka [6]) and Gliotactin (Gli [7]) are TCJ components essential for epithelial barrier formation. Additionally, the conserved four-transmembranedomain protein M6, the only myelin proteolipid protein (PLP) family member in Drosophila, localizes to TCJs [8,9]. PLPs associate with cholesterol-rich membrane domains and induce filopodia formation [10,11] and membrane curvature [12], and Drosophila M6 acts as a tumor suppressor [8], but its role in TCJ formation remained unknown.…”