Heikki Rauvala group
| Research | People | Selected publications |
Cell surface and extracellular matrix molecules in neuronal development, plasticity and disorders
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Heikki Rauvala Professor, Director P.O. Box 56, FIN-00014 University of Helsinki Phone: +358-9-191 57621 Fax: +358-9-191 57620 E-mail: heikki-dot-rauvala-at-helsinki-dot-fi |
Our group focuses on mechanisms of neuronal development and plasticity. Based on neurite outgrowth assays, we have previously isolated, cloned, and produced as recombinant proteins two ligands of heparan sulfate proteoglycans, HB-GAM (heparin-binding growth-associated molecule; pleiotrophin) and HMGB1 (high-mobility group B1; amphoterin).
Recent studies have shown that HB-GAM regulates migration of neurons in developing brain through binding to the transmembrane proteoglycan syndecan-3 (N-syndecan). Furthermore, syndecan-3 acts as a cell surface receptor for GDNF (glial cell-derived neurotrophic factor)-family neurotrophic factors.
In addition to heparin/heparan sulfates, HMGB1 binds to the immunoglobulin superfamily protein RAGE (receptor for advanced glycation end-products), which mediates the neurite outgrowth-promoting signal of HMGB1. In addition to growth cone migration, HMGB1/RAGE regulates migration and proliferation of many cell types during development, tumor spread, and inflammation. Studies using the zebrafish model have recently identified HMGB1 as an essential gene for forebrain development.
AMIGO (amphoterin-induced gene and orf) has been identified as an HMGB1-induced gene in hippocampal neurons using ordered differential display. AMIGO defines a novel gene family with three closely related members (AMIGO, AMIGO 2, and AMIGO 3) that belong to both LRR (leucine-rich repeat) and Ig (immunoglobulin) superfamilies of cell surface proteins. We have recently identified AMIGO as an auxiliary subunit of the Kv2.1 potassium channel. Furthermore, AMIGO affects the channel activity and thereby excitability of neurons.