Molecular Cloning of Syndecan, an Integral Membrane Proteoglycan

• Published in: The Journal of cell biology Vol. 108; no. 4; pp. 1547 - 1556
• Main Authors: Saunders, Scott, Jalkanen, Markku, O'Farrell, Susan, Bernfield, Merton
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.04.1989; The Rockefeller University Press
• Subjects: Amino Acid Sequence; Amino acids; Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Binding Sites; Biological and medical sciences; Blotting, Northern; Cell Line; Cell Membrane - metabolism; Cells; Chondroitin Sulfates - metabolism; Cloning, Molecular; Complementary DNA; DNA - genetics; Epithelial cells; Female; Fundamental and applied biological sciences. Psychology; Glycoproteins; Heparitin Sulfate - metabolism; Integrins; Mammary Glands, Animal; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Messenger RNA; Mice; Molecular Sequence Data; Proteins; Proteoglycans; Receptors; Restriction Mapping; RNA; Sequence Homology, Nucleic Acid; Sulfates; Syndecans; Proteoglycan; Membrane protein; Intrinsic protein; Rodentia; Glycoproteins; Gene library; Cell surface; Northern blotting; Vertebrata; Mammalia; Complementary DNA; Mouse; Plasma membrane; Mammary gland; Molecular cloning; Aminoacid sequence
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.108.4.1547

We describe cDNA clones for a cell surface proteoglycan that bears both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix. The cDNA encodes a unique core protein of 32,868 D that contains several structural features consistent with its role as a glycosaminoglycan-containing matrix anchor. The sequence shows discrete cytoplasmic, transmembrane, and NH2-terminal extracellular domains, indicating that the molecule is a type I integral membrane protein. The cytoplasmic domain is small and similar in size but not in sequence to that of the β-chain of various integrins. The extracellular domain contains a single dibasic sequence adjacent to the extracellular face of the transmembrane domain, potentially serving as the protease-susceptible site involved in release of this domain from the cell surface. The extracellular domain contains two distinct types of putative glycosaminoglycan attachment sites; one type shows sequence characteristics of the sites previously described for chondroitin sulfate attachment, but the other type has newly identified sequence characteristics that potentially correspond to heparan sulfate attachment sites. The single N-linked sugar recognition sequence is within the putative chondroitin sulfate attachment sequence, suggesting asparagine glycosylation as a mechanism for regulating chondroitin sulfate chain addition. Both 5′ and 3′ regions of this cDNA have sequences substantially identical to analogous regions of the human insulin receptor cDNA: a 99-bp region spanning the 5′ untranslated and initial coding sequences is 67% identical and a 35-bp region in the 3′ untranslated region is 81% identical in sequence. mRNA expression is tissue specific; various epithelial tissues show the same two sizes of mRNA (2.6 and 3.4 kb); in the same relative abundance (3:1), the cerebrum shows a single 4.5-kb mRNA. This core protein cDNA describes a new class of molecule, an integral membrane proteoglycan, that we propose to name syndecan (from the Greek syndein, to bind together).