An adhesion molecule in free‐living Dictyostelium amoebae with integrin β features

Macropinocytosis is an ancient mechanism that allows cells to harvest nutrients from extracellular media, which also allows immune cells to sample antigens from their surroundings. During macropinosome formation, bulk plasma membrane is internalized with all its integral proteins. It is vital for cells to salvage these proteins before degradation, but the mechanisms for sorting them are not known. Here we describe the evolutionarily conserved recruitment of the WASH (WASP and SCAR homolog) complex to both macropinosomes and phagosomes within a minute of internalization. Using Dictyostelium, we demonstrate that WASH drives protein sorting and recycling from macropinosomes and is thus essential to maintain surface receptor levels and sustain phagocytosis. WASH functionally interacts with the retromer complex at both early and late phases of macropinosome maturation, but mediates recycling via retromer-dependent and -independent pathways. WASH mutants consequently have decreased membrane levels of integrins and other surface proteins. This study reveals an important pathway enabling cells to sustain macropinocytosis without bulk degradation of plasma membrane components.phagocytosis | macropinocytosis | WASH | Dictyostelium | trafficking

Section: Wash Drives Recycling Of Surface Proteins From Early Macropisupporting

confidence: 68%

WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

Buckley

Gopaldass

Bosmani

et al. 2016

“…3). For example, it has been shown that the talin homolog of the amoebozoan D. discoideum interacts with an NPXY motif (the same motif found in integrin β) of the cytoplasmic tail of an adhesion molecule called SibA (45). Thus, it is possible that an ancestral integrin β independently acquired an NPXY motif allowing it to recruit talin.…”

Section: Discussionmentioning

confidence: 99%

Ancient origin of the integrin-mediated adhesion and signaling machinery

Sebé-Pedrós

Roger

Lang

et al. 2010

223

273

The evolution of animals (metazoans) from their unicellular ancestors required the emergence of novel mechanisms for cell adhesion and cell-cell communication. One of the most important cell adhesion mechanisms for metazoan development is integrinmediated adhesion and signaling. The integrin adhesion complex mediates critical interactions between cells and the extracellular matrix, modulating several aspects of cell physiology. To date this machinery has been considered strictly metazoan specific. Here we report the results of a comparative genomic analysis of the integrin adhesion machinery, using genomic data from several unicellular relatives of Metazoa and Fungi. Unexpectedly, we found that core components of the integrin adhesion complex are encoded in the genome of the apusozoan protist Amastigomonas sp., and therefore their origins predate the divergence of Opisthokonta, the clade that includes metazoans and fungi. Furthermore, our analyses suggest that key components of this apparatus have been lost independently in fungi and choanoflagellates. Our data highlight the fact that many of the key genes that had formerly been cited as crucial for metazoan origins have a much earlier origin. This underscores the importance of gene cooption in the unicellular-to-multicellular transition that led to the emergence of the Metazoa.cell adhesion | lateral gene transfer | metazoan origins | multicellularity

“…The Sib proteins are proposed to be functional homologs of the β-chain of integrin heterodimer in Dictyostelium, and talin A binds to all of the five Sib proteins in vitro (18). Specifically, SibA is shown to be important in cellsubstrate adhesion in the unicellular stage (17,18). We produced a double knockout mutant lacking both talin A and SibA (talin A/SibA-null) and found that they seldom produced long tails during chemotactic locomotion (Fig.…”

Section: Talin a Is Required For Normal Tail Retraction In Directed Cellmentioning

confidence: 99%

“…This is consistent with a model in which some adhesion molecules normally linked to the cortical cytoskeleton by talin A are not pulled off the substratum in talin Anull cells that keep advancing. SibA (17,18) is a candidate of such adhesion molecules. The Sib proteins are proposed to be functional homologs of the β-chain of integrin heterodimer in Dictyostelium, and talin A binds to all of the five Sib proteins in vitro (18).…”

Section: Talin a Is Required For Normal Tail Retraction In Directed Cellmentioning

confidence: 99%

“…SibA (17,18) is a candidate of such adhesion molecules. The Sib proteins are proposed to be functional homologs of the β-chain of integrin heterodimer in Dictyostelium, and talin A binds to all of the five Sib proteins in vitro (18). Specifically, SibA is shown to be important in cellsubstrate adhesion in the unicellular stage (17,18).…”

Section: Talin a Is Required For Normal Tail Retraction In Directed Cellmentioning

confidence: 99%

See 1 more Smart Citation

Talin couples the actomyosin cortex to the plasma membrane during rear retraction and cytokinesis

Tsujioka

Yumura

Inouye

et al. 2012

Contraction of the cortical actin cytoskeleton underlies both rear retraction in directed cell migration and cytokinesis. Here, we show that talin, a central component of focal adhesions, has a major role in these processes. We found that Dictyostelium talin A colocalized with myosin II in the rear of migrating cells and the cleavage furrow. During directed cell migration, talin A-null cells displayed a long thin tail devoid of actin filaments, whereas additional depletion of SibA, a transmembrane adhesion molecule that binds to talin A, reverted this phenotype, suggesting a requirement of the link between actomyosin and SibA by talin A for rear retraction. Disruptions of talin A also resulted in detachment of the actomyosin contractile ring from the cell membrane and concomitant regression of the cleavage furrow under certain conditions. The C-terminal actin-binding domain (ABD) of talin A exhibited a localization pattern identical to that of full-length talin A. The N-terminal FERM domain was found to bind phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] and phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] in vitro. In vivo, however, PtdIns(4,5)P2, which is known to activate talin, is believed to be enriched in the rear of migrating cells and the cleavage furrow in Dictyostelium . From these results, we propose that talin A activated by PtdIns(4,5)P2 in the cell posterior or cleavage furrow links actomyosin cytoskeleton to adhesion molecules or other membrane proteins, and that the force is transmitted through these links to retract the tail during cell migration or to cause efficient ingression of the equator during cytokinesis.