Isolation of a neuronal cell surface receptor of heparin binding growth-associated molecule (HB-GAM). Identification as N-syndecan (syndecan-3).

نویسندگان

  • E Raulo
  • M A Chernousov
  • D J Carey
  • R Nolo
  • H Rauvala
چکیده

HB-GAM (heparin binding growth-associated molecule; pleiotrophin) is a secretory, extracellular matrix-associated protein that is strongly expressed in developing nervous tissues and belongs to a novel family of differentiation/growth factors. It promotes axonal growth from perinatal rat brain neurons and is suggested to be mitogenic for some cell types and to display cell-transforming activity. Since the receptors of HB-GAM in cells are unknown, we have started isolation of putative cell surface receptors from brain neurons and from perinatal rat brain. For this purpose, recombinant HB-GAM was produced with the aid of a baculovirus vector and used as an affinity matrix in receptor isolation. A detergent-solubilized component from cultured brain neurons and from brain was identified that binds specifically to HB-GAM and migrates on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a broad smear with an apparent molecular mass of about 200 kDa. This cell surface component was found to contain heparan sulfate chains, which are bound to a core protein with an apparent molecular mass of 120 kDa. Gel electrophoretic characteristics, immunochemical analysis, and partial peptide sequencing revealed that the cell surface component isolated as an HB-GAM receptor is N-syndecan (syndecan-3). In a solid phase binding assay, N-syndecan was found to bind to HB-GAM in a similar manner as to basic fibroblast growth factor (KD = 0.6 nM). Immunofluorescence microscopy indicated that in brain neurons, N-syndecan occurs at the surface of the cell soma and of the neurites that grow along HB-GAM-coated substrates. Anti-N-syndecan antibodies added to culture media had an inhibitory effect on HB-GAM-induced neurite outgrowth. We suggest that N-syndecan mediates the neurite outgrowth-promoting signal from HB-GAM to the cytoskeleton of growing neurites.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Ligand-induced dimerization of syndecan-3 at the cell surface

Syndecan-3 (N-syndecan) is a transmembrane heparan sulfate proteoglycan abundantly expressed in developing brain. In addition to acting as a coreceptor, syndecan-3 acts as a signaling receptor upon binding of its ligand HB-GAM (heparin-binding growth-associated molecule; pleiotrophin), which activates the cortactin-src kinase signaling pathway. This leads to rapid neurite extension in neuronal ...

متن کامل

Regulation of mRNA localization by transmembrane signalling: local interaction of HB-GAM (heparin-binding growth-associated molecule) with the cell surface localizes beta-actin mRNA.

Localization of mRNAs is currently thought to be partially responsible for molecular sorting to specific compartments within the cell. In mammalian cells the best-studied example is the beta-actin mRNA that is localized to the cell processes, and its localization is necessary in migratory responses of cells. It is reasonable to assume that mRNA localization within cells is coupled to transmembr...

متن کامل

N-syndecan deficiency impairs neural migration in brain

N-syndecan (syndecan-3) is a transmembrane proteoglycan that is abundantly expressed in the major axonal pathways and in the migratory routes of the developing brain. When ligated by heparin-binding (HB) growth-associated molecule (GAM; pleiotrophin), N-syndecan mediates cortactin-Src kinase-dependent neurite outgrowth. However, the functional role of N-syndecan in brain development remains une...

متن کامل

Heparin-binding growth-associated molecule (HB-GAM) in activity-dependent neuronal plasticity in hippocampus

Academic Dissertation To be presented for public criticism, with the permission of the Role of heparin-binding growth-associated molecule (HB-GAM) in hippocampal LTP and spatial learning revealed by studies on overexpressing and knockout mice. Syndecan-3-deficient mice exhibit enhanced LTP and impaired hippocampus-dependent memory. Mol Rauvala H. The two thrombospondin type I repeat domains of ...

متن کامل

Osteoblast Recruitment and Bone Formation Enhanced by Cell Matrix–associated Heparin-binding Growth-associated Molecule (HB-GAM)

Bone has an enormous capacity for growth, regeneration, and remodeling. This capacity is largely due to induction of osteoblasts that are recruited to the site of bone formation. The recruitment of osteoblasts has not been fully elucidated, though the immediate environment of the cells is likely to play a role via cell- matrix interactions. We show here that heparin-binding growth-associated mo...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of biological chemistry

دوره 269 17  شماره 

صفحات  -

تاریخ انتشار 1994