9.A.35 The Peptide Translocating Syndecan (Syndecan) Family
Syndecans are transmembrane heparan sulfate proteoglycans. They are implicated in the binding of extracellular matrix components and growth factors. Syndecan is made as a precursor with a hydrophobic N-terminal leader peptide and a strongly hydrophobic TMS which presumably anchors the protein in the membrane. Its oligomeric structure is unknown. Syndecan-4 and beta1 integrin protein levels and their localization in costameric structures are regulated by electrical activity by a mechanism that influences the adhesion properties of skeletal myotubes during differentiation (Ugarte et al. 2010).
Cell-penetrating peptides (CPPs) are short peptides capable of translocating across the plasma membrane of live cells and transporting conjugated compounds intracellularly. The first model cationic CPPs to be discovered were penetratin and TAT. CPPs may enter cells by mediation using a surface receptor. Letoha et al. (2010) reported that syndecan-4, the universally expressed isoform of the syndecan family of transmembrane proteoglycans, binds and mediates transport of the three most frequently utilized cationic CPPs (penetratin, octaarginine and TAT) into the cells. Quantitative uptake studies and mutational analyses demonstrate that attachment of the cationic CPPs is mediated by specific interactions between the heparan sulfate chains of syndecan-4 and the CPPs. Protein kinase C alpha is also involved in uptake. The data presented by Letoha et al. (2010) provide direct evidence for the receptor-mediated uptake of cationic CPPs.
Syndecan-4 of 198 aas. Cell surface proteoglycan that bears heparan sulfate. Regulates exosome biogenesis in concert with SDCBP and PDCD6IP. The syndecan-syntenin-ALIX complex plays a role in membrane transport and signalling processes (Baietti et al. 2012).
Syndecan-4 of Homo sapiens (P31431)
Syndecan-1 of 310 aas and 2 TMSs, N- and C-terminal. The binding of cytokines and growth factors to heparan sulfate (HS) chains on proteoglycans generates gradients that control development and regulate wound healing. Syndecan-1 (sdc1) is an integral membrane HS proteoglycan. Its structure allows it to bind with cytosolic, transmembrane, and extracellular matrix (ECM) proteins. It plays important roles in mediating key events during wound healing because it regulates a number of important processes, including cell adhesion, cell migration, endocytosis, exosome formation, and fibrosis (Stepp et al. 2015).
Syndecan-1 of Homo sapiens