Thrombospondins as key regulators of synaptogenesis in the central nervous system

Abstract

Thrombospondins (TSPs) are a family of large, oligomeric multidomain glycoproteins that participate in a variety of biological functions as part of the extracellular matrix (ECM). Through their associations with a number of binding partners, TSPs mediate complex cell-cell and cell-matrix interactions in such diverse processes as angiogenesis, inflammation, osteogenesis, cell proliferation, and apoptosis. It was recently shown in the developing central nervous system (CNS) that TSPs promote the formation of new synapses, which are the unique cell-cell adhesions between neurons in the brain. This increase in synaptogenesis is mediated by the interaction between astrocyte-secreted TSPs and their neuronal receptor, calcium channel subunit α2δ-1. The cellular and molecular mechanisms that underlie induction of synaptogenesis via this interaction are yet to be fully elucidated. This review will focus on what is known about TSP and synapse formation during development, possible roles for TSP following brain injury, and what the previously established actions of TSP in other biological tissues may tell us about the mechanisms underlying TSP’s functions in CNS synaptogenesis.

Thrombospondin-1 prevents amyloid beta–mediated synaptic pathology in Alzheimer's disease

“…6). Several studies have demonstrated the importance of the TSP-1-a2d1 interaction in synaptogenesis; however, the mechanism by which the a2d1 ligands including TSP-1 participates in synaptogenesis remains unclear (Eroglu et al, 2009;Risher and Eroglu, 2012). Kurshan et al (2009) showed that a2d1 may act through cytoskeletal rearrangements, and regulation of the cytoskeleton is known to be important for synaptic spine formation.…”

The role of G protein-coupled receptors in the early evolution of neurotransmission and the nervous system

“…PDZ domains are protein-interaction domains that are concentrated in the postsynaptic density and regulate synaptic transmission (Kim and Sheng, 2004). Furthermore, the N-termini of BAIs encodes thrombospondin type 1 repeats (TSRs), which regulate synaptogenesis and neural development (Adams and Tucker, 2000;Risher and Eroglu, 2012). These TRS repeats act as major interacting regions for BAI interaction partners, including the C1q-like proteins (Bolliger et al, 2011), which are highly expressed in the CNS and aid in synapse formation (Yuzaki, 2010).…”

Invoking the power of thrombospondins: Regulation of thrombospondins expression

“…Regulation of angiogenesis and cancer progression (12), regulation of inflammation (8, 13-16), modulation of immune response (17, 18), formation of myotendinous junctions (19), maintenance of the myocardium integrity and function (20-27), regulation of fibrosis (28), and synaptogenesis (29) are just a few examples of their roles in physiology and pathology. To participate in the critical physiological processes, TSPs have to be present in the right location at the right time.…”