Evidence for intercellular communication in mosquito renal tubules: A putative role of gap junctions in coordinating and regulating the rapid diuretic effects of neuropeptides

Abstract

Adult female mosquitoes require a blood meal from a vertebrate host to successfully reproduce. During a single blood feeding, a female may ingest more than the equivalent of her own body mass, resulting in an acute stress to osmotic and ionic homeostasis. In response to this stress, the renal (Malpighian) tubules mediate a rapid diuresis that commences as soon as blood is ingested. The diuresis is regulated by neuropeptides (e.g., kinins, calcitonin-like peptide) that act on receptors in the Malpighian tubule epithelium. Interestingly, the expression of these receptors is discontinuous throughout the epithelium, which raises the question as to how Malpighian tubules mount such a rapid and synchronized response to neuropeptide stimulation. Here we propose a hypothesis that gap junctions functionally couple the epithelial cells of Malpighian tubules, resulting in a coordinated physiological response to the binding of neuropeptides. We review recent, relevant literature on the electrophysiology, physiology, and molecular biology of mosquito Malpighian tubules that indicate the presence of gap junctions in the epithelium. We also provide new physiological and immunochemical data that are consistent with the proposed hypothesis.

The molecular and immunochemical expression of innexins in the yellow fever mosquito, Aedes aegypti: Insights into putative life stage- and tissue-specific functions of gap junctions

“…Our laboratory is especially interested in the putative roles of innexins in the synchronization and regulation of renal functions in adult female mosquitoes (Piermarini and Calkins 2013). Thus, we aimed to clone the AeInx cDNAs (and any splice variants) expressed in female Malpighian tubules ( AeInx1 , AeInx2 , AeInx3 , and AeInx7 ; Figure 2) and elucidate their respective gene structures.…”

“…Thus, AeInx3 in principal cells has the potential to dock with opposing innexins in stellate cells and form heterotypic GJ. Additional experiments will be necessary to determine the identity of such innexin(s) in stellate cells, which would help support the hypothesis that stellate and principal cells are functionally coupled (Beyenbach and Piermarini, 2011; Piermarini and Calkins, 2013; Piermarini et al, 2010). …”

“…Moreover, innexin 4 ( zero population growth or zpg ) is involved with functional gonad formation in males of both D. melanogaster flies and Anopheles gambiae mosquitoes (Magnusson et al, 2011; Tazuke et al, 2002), and is necessary for early germ cell differentiation in female D. melanogaster (Gilboa et al, 2003). Furthermore, innexins are likely responsible for the functional coupling of epithelial cells in the renal (Malpighian) tubules of mosquitoes (Beyenbach and Piermarini, 2011; Piermarini and Calkins, 2013; Weng et al, 2008). …”

The rectal complex and Malpighian tubules of the cabbage looper (Trichoplusia ni): regional variations in Na+ and K+ transport and cation reabsorption by secondary cells

“…NHA2 may mediate transport of Na + and K + from cell to lumen. Alternatively, gap junctions may functionally couple stellate and principal cells (Beyenbach et al, 2010;Calkins et al, 2015;Piermarini and Calkins, 2014), thus allowing principal cells to secrete K + that enters stellate cells through AeKir1 . In contrast to our extensive knowledge of stellate cells in tubules of dipterans, little is known of secondary cell transporters and their functions in lepidopteran tubules.…”

Intracellular dynamics of polydnavirus innexin homologues

“…The Innexins are largely supposed to function through formation of hemichannels, which form gap junctions to generate intercellular channels. Gap junctions are present and active in nearly all insect physiological systems, where transfer of small molecules has been observed or is predicted to affect system processes including Malpighian tubule activity (Weng et al, 2008;Piermarini and Calkins, 2014), oocyte patterning and provisioning (Adler and Woodruff, 2000;Anderson and Woodruff, 2001;Bohrmann and Zimmermann, 2008;Kruger and Bohrmann, 2015) and electrical synapse connectivity (Phelan et al, 1996;Phelan et al, 2008;Anava et al, 2009;Anava et al, 2013). Gap junctions also have been observed in the immune system of insects, particularly during transient and continuous contact of haemocytes (Baerwald, 1975;Baerwald, 1979;Caveney and Berdan, 1982;Churchill et al, 1993), while functional data implicate them in haemolytic (Hasegawa et al, 2017) and gut immunity (Li et al, 2014b).…”