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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.

References associated with 9.A.35 family:

Baietti, M.F., Z. Zhang, E. Mortier, A. Melchior, G. Degeest, A. Geeraerts, Y. Ivarsson, F. Depoortere, C. Coomans, E. Vermeiren, P. Zimmermann, and G. David. (2012). Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 14: 677-685. 22660413
Letoha T., Keller-Pinter A., Kusz E., Kolozsi C., Bozso Z., Toth G., Vizler C., Olah Z. and Szilak L. (2010). Cell-penetrating peptide exploited syndecans. Biochim Biophys Acta. 1798(12):2258-65. 20138023
Stepp, M.A., S. Pal-Ghosh, G. Tadvalkar, and A. Pajoohesh-Ganji. (2015). Syndecan-1 and Its Expanding List of Contacts. Adv Wound Care (New Rochelle) 4: 235-249. 25945286
Sundberg, E.L., Y. Deng, and C.G. Burd. (2019). Syndecan-1 Mediates Sorting of Soluble Lipoprotein Lipase with Sphingomyelin-Rich Membrane in the Golgi Apparatus. Dev Cell. [Epub: Ahead of Print] 31543446
Ugarte, G., C. Santander, and E. Brandan. (2010). Syndecan-4 and beta1 integrin are regulated by electrical activity in skeletal muscle: Implications for cell adhesion. Matrix Biol 29: 383-392. 20362053