Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function

Abstract

Tetraspanins (Tspans) comprise a membrane protein family structurally defined by four transmembrane domains and intracellular N and C termini that is found in almost all cell types and tissues of eukaryotes. Moreover, they are involved in a bewildering multitude of diverse biological processes such as cell adhesion, motility, protein trafficking, signaling, proliferation, and regulation of the immune system. Beside their physiological roles, they are linked to many pathophysiological phenomena, including tumor progression regulation, HIV-1 replication, diabetes, and hepatitis. Tetraspanins are involved in the formation of extensive protein networks, through interactions not only with themselves but also with numerous other specific proteins, including regulatory proteins in the central nervous system (CNS). Interestingly, recent studies showed that Tspan7 impacts dendritic spine formation, glutamatergic synaptic transmission and plasticity, and that Tspan6 is correlated with epilepsy and intellectual disability (formerly known as mental retardation), highlighting the importance of particular tetraspanins and their involvement in critical processes in the CNS. In this review, we summarize the current knowledge of tetraspanin functions in the brain, with a particular focus on their impact on glutamatergic neurotransmission. In addition, we compare available resolved structures of tetraspanin family members to those of auxiliary proteins of glutamate receptors that are known for their modulatory effects.

ExoJ: an ImageJ2/Fiji plugin for automated spatiotemporal detection and analysis of exocytosis

“…We next sought to investigate the exocytic dynamics of vesicle subpopulations. TSPAN CD9, CD63 and CD81 are known to form protein microdomains at the PM [54, 55] regulating various cellular function ranging from cell adhesion to proliferation [56] and signaling at the immune synapse [57]. Recently, these three TSPANs are found to be enriched to various degrees in the membrane of EV subpopulations such as ectosomes and exosomes.…”

“…We next evaluated whether ExoJ could be used to quantitatively study exocytosis. TSPAN CD9, CD63 and CD81 are known to form protein microdomains at the PM (Hemler, 2005; le Naour et al, 2006) regulating various cellular function ranging from cell adhesion to proliferation (Becic et al, 2022) and signaling at the immunological synapse (Levy and Shoham, 2005). Recently, these three TSPANs are found to be enriched to various degrees in the membrane of EV subpopulations such as ectosomes and exosomes (Crescitelli et al, 2013; Escola et al, 1998; Kowal et al, 2016; Mathieu et al, 2021; Théry et al, 2018; Verweij et al, 2018).…”

MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size

“…Of the miR-4707-3p targets predicted via TargetScan (66), 13 were consistently downregulated in mir-4707 samples as compared to control samples in both weeks one and two (Figure 6D). Among these are the gamma- aminobutyric acid (GABA) transporter, SLC6A1 (also known as GAT1), found in presynaptic terminals, NDRG2 and SORCS2, both with known roles in neurite outgrowth and branching, and TSPAN6, which interacts with glutamate receptors, mediates synaptic transmission and is associated with epilepsy and intellectual disability (67–71). These results suggest that miR- 4707-3p has a direct effect on synapse maturation in differentiating human neural progenitors.…”

Modulation of Notch Signaling at Early Stages of Differentiation of Human Induced Pluripotent Stem Cells to Dopaminergic Neurons

“…S100beta protein is expressed predominantly in astrocytes, but it has been shown to play an important role in growth regulation. TSPAN7 is known to play role in regulation of cell migration [ 20 ], AMPA receptor internalization and cerebellum development, especially for cerebellar granule cell axonal branching [ 14 ].…”