FLN-1/Filamin is required to anchor the actomyosin cytoskeleton and for global organization of sub-cellular organelles in a contractile tissue

Kelley, Charlotte A.; Triplett, Olivia; Mallick, Samyukta; Burkewitz, Kristopher; Mair, William; Cram, Erin J.

doi:10.1101/2020.07.03.186965

Cited by 1 publication

(1 citation statement)

References 127 publications

(125 reference statements)

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“…In D.melanogaster , Cheerio (type 1 filamin) is involved in mechanotransduction during egg development (100), and tissue remodelling of the epithelium during development (101), while Jitterbug (type 2 filamin) regulates axon migration and targeting during neural development (102), and the formation of actin-rich protrusions (bristles) on the epithelium (68). In C.elegans , FLN-1 is involved in actin remodelling in the spermatheca during reproduction (103, 104), and FLN-2 is involved in biogenesis of multivesicular bodies that associate with lysosomes (105), and interestingly, its loss of function increases life span in animals that experience pharyngeal infections (106).…”

Section: Discussionmentioning

confidence: 99%

Function and phylogeny support the independent evolution of acid-sensing ion channels in the Placozoa

Elkhatib

Yáñez-Guerra

Mayorova

et al. 2022

Preprint

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Acid-sensing ion channels (ASICs) are proton-gated cation channels that are part of the Deg/ENaC ion channel family, which also includes neuropeptide-, bile acid-, and mechanically-gated channels. Despite sharing common tertiary and quaternary structures, strong sequence divergence within the Deg/ENaC family has made it difficult to resolve their phylogenetic relationships, and by extension, whether channels with common functional features, such as proton-activation, share common ancestry or evolved independently. Here, we report that a Deg/ENaC channel from the early diverging placozoan species Trichoplax adhaerens, named TadNaC2, conducts proton-activated currents in vitro with biophysical features that resemble those of the mammalian ASIC1 to ASIC3 channels. Through a combined cluster-based and phylogenetic analysis, we successfully resolve the evolutionary relationships of most major lineages of metazoan Deg/ENaC channels, identifying two subfamilies within the larger Deg/ENaC family that are of ancient, pre-bilaterian origin. We also identify bona fide Deg/ENaC channel homologues from filasterean and heterokont single celled eukaryotes. Furthermore, we find that ASIC channels, TadNaC2, and various other proton-activated channels from vertebrates and invertebrates are part of phylogenetically distinct lineages. Through structural modelling and mutation analysis, we find that TadNaC2 proton-activation employs fundamentally different molecular determinants than ASIC channels, and identify two unique histidine residues in the placozoan channel that are required for its proton-activation. Together, our phylogenetic and functional analyses support the independent evolution of proton-activated channels in the phylum Placozoa. Spurred by our discovery of pH sensitive channels, we discovered that despite lacking a nervous system, Trichoplax can sense changes in extracellular pH to coordinate its various cell types to locomote away from acidic environments, and to contract upon rapid exposure to acidic pH in a Ca2+-dependent manner. Lastly, via yeast 2 hybrid screening, we find that the Trichoplax channels TadNaC2 and TadNaC10, belonging to the two separate Deg/ENaC subfamilies, interact with the cytoskeleton organizing protein filamin, similar to the interaction reported for the human ENaC channels.

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