CD81 Promotes a Migratory Phenotype in Neuronal-Like Cells

Abstract

Tetraspanins, such as CD81, can form lateral associations with each other and with other transmembrane proteins. These interactions may underlie CD81 functions in multiple cellular processes, such as adhesion, morphology, migration, and differentiation. Since CD81's role in neuronal cells’ migration has not been established, we here evaluated effects of CD81 on the migratory phenotype of SH-SY5Y neuroblastoma cells. CD81 was found enriched at SH-SY5Y cell's membrane, co-localizing with its interactor filamentous-actin (F-actin) in migratory relevant structures of the leading edge (filopodia, stress fibers, and adhesion sites). CD81 overexpression increased the number of cells with a migratory phenotype, in a potentially phosphatidylinositol 3 kinase (PI3K)–Ak strain transforming (AKT) mediated manner. Indeed, CD81 also co-localized with AKT, a CD81-interactor and actin remodeling agent, at the inner leaflet of the plasma membrane. Pharmacologic inhibition of PI3K, the canonical AKT activator, led both to a decrease in the acquisition of a migratory phenotype and to a redistribution of intracellular CD81 and F-actin into cytoplasmic agglomerates. These findings suggest that in neuronal-like cells CD81 bridges active AKT and actin, promoting the actin remodeling that leads to a motile cell morphology. Further studies on this CD81-mediated mechanism will improve our knowledge on important physiological and pathological processes such as cell migration and differentiation, and tumor metastasis.

Microglia undergo transcriptional, translational and functional adaptations to dark and light phases in laboratory mice

“…Importantly, CCT5 interacts with F-actin enabling proper MERTK-dependent phagocytic functions (Feng et al, 2022). Furthermore, CD81 was enriched during the active phase ( Table S5 ), a protein relevant for microglia motility and myelin phagocytosis (Martins et al, 2019). The proteotype analysis also revealed a decrease in P2Y12 and CD39 levels during the sleep phase, as were the corresponding transcripts ( Table S5 ), confirming a circadian regulation of the microglial purinergic system.…”

APP Binds to the EGFR Ligands HB-EGF and EGF, Acting Synergistically with EGF to Promote ERK Signaling and Neuritogenesis

“…The interaction with CD9 modulates PM-anchored HB-EGF juxtacrine actions, cleavage to the mature form, and internalization [17,66]. Interestingly, APP also forms complexes with α3β1 Itg and CD81 to mediate cell/growth cone adhesion [10,67], and with α3β1 Itg and Reelin to mediate hippocampal dendritic outgrowth [9]. Thus, the formation of cis-and trans-heterodimers between APP and pro-HB-EGF might be mediated by HSPG, integrins and tetraspanins, and are expected to have a role in (neural) cell adhesion, migration and neuritogenesis.…”