Regulation of the Scar/WAVE complex in migrating cells: A summary of our understanding

Singh, Shashi P.

doi:10.1007/s12038-023-00341-7

Cited by 1 publication

(1 citation statement)

References 120 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, we showed that C3G promoted actin polymerization during spreading on CRP-XL, but not on fibrinogen. C3G did this by modulating Rac1 activity and by interacting with proteins involved in actin remodeling during lamellipodia formation, such as WAVE2, Arp2/3, Abi1 and VASP [ 60 ]. Notably, this function of C3G is independent of Rap1, despite the described role of Rap1b in platelet spreading [ 61 ] via Rac1 [ 25 ] (Fig.…”

Section: Discussionmentioning

confidence: 99%

Platelet C3G: a key player in vesicle exocytosis, spreading and clot retraction

Fernández-Infante,

Hernández-Cano,

Herranz

et al. 2024

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

C3G is a Rap1 GEF that plays a pivotal role in platelet-mediated processes such as angiogenesis, tumor growth, and metastasis by modulating the platelet secretome. Here, we explore the mechanisms through which C3G governs platelet secretion. For this, we utilized animal models featuring either overexpression or deletion of C3G in platelets, as well as PC12 cell clones expressing C3G mutants. We found that C3G specifically regulates α-granule secretion via PKCδ, but it does not affect δ-granules or lysosomes. C3G activated RalA through a GEF-dependent mechanism, facilitating vesicle docking, while interfering with the formation of the trans-SNARE complex, thereby restricting vesicle fusion. Furthermore, C3G promotes the formation of lamellipodia during platelet spreading on specific substrates by enhancing actin polymerization via Src and Rac1-Arp2/3 pathways, but not Rap1. Consequently, C3G deletion in platelets favored kiss-and-run exocytosis. C3G also controlled granule secretion in PC12 cells, including pore formation. Additionally, C3G-deficient platelets exhibited reduced phosphatidylserine exposure, resulting in decreased thrombin generation, which along with defective actin polymerization and spreading, led to impaired clot retraction. In summary, platelet C3G plays a dual role by facilitating platelet spreading and clot retraction through the promotion of outside-in signaling while concurrently downregulating α-granule secretion by restricting granule fusion.

show abstract

Section: Discussionmentioning

confidence: 99%