Guidance of subcellular tubulogenesis by actin under the control of a synaptotagmin-like protein and Moesin

Abstract

Apical membranes in many polarized epithelial cells show specialized morphological adaptations that fulfil distinct physiological functions. The air-transporting tubules of Drosophila tracheal terminal cells represent an extreme case of membrane specialization. Here we show that Bitesize (Btsz), a synaptotagmin-like protein family member, is needed for luminal membrane morphogenesis. Unlike in multicellular tubes and other epithelia, where it influences apical integrity by affecting adherens junctions, Btsz here acts at a distance from junctions. Localized at the luminal membrane through its tandem C2 domain, it recruits activated Moesin. Both proteins are needed for the integrity of the actin cytoskeleton at the luminal membrane, but not for other pools of F-actin in the cell, nor do actin-dependent processes at the outer membrane, such as filopodial activity or membrane growth depend on Btsz. Btsz and Moesin guide luminal membrane morphogenesis through organizing actin and allowing the incorporation of membrane containing the apical determinant Crumbs.

Intracellular lumen formation in Drosophila proceeds via a novel subcellular compartment

“…3A,B). Although there is evidence that actin matrices underlie organization of both the basal and apical plasma membranes in terminal cells (Gervais and Casanova, 2010;JayaNandanan et al, 2014;Levi et al, 2006;Schottenfeld-Roames et al, 2014;Ukken et al, 2014), we do not observe such matrices, probably because our fixation methods do not preserve these particular cytoskeletal elements. The features we observe are consistent with previous reports of tracheolar ultrastructure, observed in Drosophila and other insects fixed using standard chemical techniques, but with an increased resolution of cellular membranes (Levi et al, 2006;Manning and Krasnow, 1993;Noirot and Noirot-Timothee, 1982;Snelling et al, 2011).…”

“…This model specifically proposes that vesicles are generated within the terminal cell cytoplasm, move to the center of each subcellular branch, and undergo fusion to form the continuous luminal membrane (Lubarsky and Krasnow, 2003). A role for vesicle trafficking in terminal cell lumen formation is bolstered by observations showing that a number of vesicle fusion and trafficking genes are required for the lumen formation process (Baer et al, 2013;Ghabrial et al, 2011;Jarecki et al, 1999;JayaNandanan et al, 2014;Jones et al, 2014;Schottenfeld-Roames and Ghabrial, 2012;SchottenfeldRoames et al, 2014). However, the sources of the vesicles required for lumen formation are not known, nor have vesicles been directly observed fusing to form the mature membrane.…”

Shaping of biological tubes by mechanical interaction of cell and extracellular matrix

“…A series of studies of tube elongation defective mutants [8,21] have shown that axial growth requires the septate junction [22][23][24][25][26][27][28][29], subapical protein complex [20,30,31], planar cell polarity proteins [32], and Src kinase [33 ,34 ]. With the exception of Src kinases, all known tube length mutants show over-elongation phenotypes.…”

The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity

“…ERM-1: ERM proteins are membrane-actin linkers with broad roles in cortical membrane organization (Neisch and Fehon 2011) and intracellular tubulogenesis (JayaNandanan et al 2014;Jiang et al 2014). ERM-1 localizes near the apical membrane and is essential for terminal web organization and for both apical and basal canal outgrowth (Khan et al 2013) ( Figure 6D, Figure 7).…”