Pathways & interactions
Short name: Syndecan
The syndecans are transmembrane proteoglycans which are involved in the organisation of cytoskeleton and/or actin microfilaments, and have important roles as cell surface receptors during cell-cell and/or cell-matrix interactions [PMID: 1335744, PMID: 8370471].
Structurally, these proteins consist of four separate domains:
- A signal sequence;
- An extracellular domain (ectodomain) of variable length whose sequence is not evolutionary conserved in the various forms of syndecans. The ectodomain contains the sites of attachment of the heparan sulphate glycosaminoglycan side chains;
- A transmembrane region;
- A highly conserved cytoplasmic domain of about 30 to 35 residues, which could interact with cytoskeletal proteins.
The proteins known to belong to this family are:
- Syndecan 1.
- Syndecan 2 or fibroglycan.
- Syndecan 3 or neuroglycan or N-syndecan.
- Syndecan 4 or amphiglycan or ryudocan.
- Drosophila syndecan.
- Caenorhabditis elegans probable syndecan (F57C7.3).
Syndecan-4, a transmembrane heparan sulphate proteoglycan, is a coreceptor with integrins in cell adhesion. It has been suggested to form a ternary signalling complex with protein kinase Calpha and phosphatidylinositol 4,5-bisphosphate (PIP2). Structural studies have demonstrated that the cytoplasmic domain undergoes a conformational transition and forms a symmetric dimer in the presence of phospholipid activator PIP2, and whose overall structure in solution exhibits a twisted clamp shape having a cavity in the centre of dimeric interface. In addition, it has been observed that the syndecan-4 variable domain interacts, strongly, not only with fatty acyl groups but also the anionic head group of PIP2. These findings indicate that PIP2 promotes oligomerisation of the syndecan-4 cytoplasmic domain for transmembrane signalling and cell-matrix adhesion [PMID: 9582338, PMID: 11456484].