CyrA, a matricellular protein that modulates cell motility in Dictyostelium discoideum

Matricellular Signal Transduction Involving Calmodulin in the Social Amoebozoan Dictyostelium

“…CyrA, which binds to CaM both in the presence and absence of calcium ions (Ca 2+ ), is secreted during growth and development [27]. In keeping with it being a secreted protein, both CyrA immunolocalization and CyrA-GFP localization showed that the protein localizes to the endoplasmic reticulum, particularly its perinuclear component [28]. Western blot analyses revealed that the intracellular expression of full-length CyrA (~63kDa) peaks between 12 and 16 hours of development, the time when multicellular slug formation occurs (Figure 1, B) [28].…”

“…In keeping with it being a secreted protein, both CyrA immunolocalization and CyrA-GFP localization showed that the protein localizes to the endoplasmic reticulum, particularly its perinuclear component [28]. Western blot analyses revealed that the intracellular expression of full-length CyrA (~63kDa) peaks between 12 and 16 hours of development, the time when multicellular slug formation occurs (Figure 1, B) [28]. At this time, CyrA is secreted at very high levels and localizes to the ECM ( i.e ., sheath) of the migrating slug.…”

“…In various experiments cells were treated with pharmacological agents: LY294002 (PI3K inhibitor), quinacrine (PLA2 inhibitor), W7 (CaM inhibitor), and TMB-8 (intracellular calcium release inhibitor). Pharmacological intervention yielded insight into the regulation of CyrA secretion by showing that it was dependent on intracellular Ca 2+ release as well as active CaM, phosphatidylinositol 3 kinase (PI3K), and phospholipase A2 (PLA2) function [28]. …”

“…The over-expression of CyrA also increases the rate of cAMP-mediated chemotaxis, providing in vivo in vivo support for the role of CyrA as a normal mediator of cell movement and cAMP chemotaxis in Dictyostelium [28]. EGFL1 is not a chemoattractant for Dictyostelium cells, however it does activate signaling pathways that function in a supportive role to increase the rate of both random cell movement and cAMP chemotaxis during development [33].…”

“…Other work has identified a group of soluble, mobile glycoproteins that localize within the sheath but their identity has not been determined [25,26]. More recently, the protein CyrA has been identified as another ECM component in Dictyostelium [27,28]. …”