The Department of Biomedicine

BBB seminar: Jyrki Heino

The role of integrin clustering in signal transduction by collagen receptors

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Jyrki Heino
Department of Biochemistry and Food Chemistry, University of Turku, Finland

Integrins are a large family of cell adhesion receptors. In addition to anchoring cells to the extracellular matrix, they mediate ligand-dependent signals into the cells. This is called "outside-in signaling". The activity of integrins can also be regulated by intracellular proteins binding to the cytoplasmic domains of integrins, often called "inside-out signaling". Recent studies have partially solved the structural bases of integrin signaling by showing the conformational changes taking place in integrin heterodimers after ligand binding and during the regulation of ligand binding activity. We have studied the collagen receptor subfamily of integrins, especially integrin alpha2beta1. The collagen receptors interact with multivalent ligands, which may induce the clustering of the integrins. Our recent results show that during "inside-out" and "outside-in" signaling, both clustering and conformation changes in individual receptors may play a critical role.

Recent papers:
M. Huhtala, J. Heino, D. Casciari, A. de Luice, and M.S. Johnson (2005) Integrin evolution: insights from ascidian and teleost fish genomes. Matrix Biol. 24: 83-95.
J. Käpylä, J. Jäälinoja, M. Tulla, J. Ylöstalo, L. Nissinen, T. Viitasalo, A-M. Säämänen, P. Vehviläinen, V. Marjomäki, R.W. Farndale, D. Birk, L. Ala-Kokko, and J. Heino (2004) The fibril associated collagen IX provides a novel mechanism for cell adhesion to cartilaginous matrix. J Biol Chem, 279: 51677-87.
J. Jokinen, E. Dadu, P. Nykvist, J. Käpylä, D.J. White, J. Ivaska, P. Vehviläinen, H. Reunanen, H. Larjava, L. Häkkinen, and J. Heino (2004) Integrin-mediated cell adhesion to type I collagen fibrils. J Biol Chem. 279: 31956-63.
L. Xing, M. Huhtala, V. Pietiäinen, J. Käpylä, K. Vuorinen, V. Marjomäki, J. Heino, M.S. Johnson, T. Hyypiä, and R.H. Cheng (2004) Structural and functional analysis of integrin alpha2I domain interaction with echovirus 1. J Biol Chem. 279: 11632-8.
Y. Nymalm, J.S. Puranen, T. K.M. Nyholm, J. Käpylä, H. Kidron, O.T. Pentikäinen, T.T. Airenne, J. Heino, J.P. Slotte, M:S. Johnson, and T.A. Salminen (2004) Jararhagin-derived RKKH-peptides induce structural changes in alpha1 I domain of human integrin alpha1beta1. J Biol Chem. 279: 7962-70.
P. Upla, V. Marjomäki, P. Kankaanpää, J. Ivaska, T. Hyypiä, F.G. van der Goot and J. Heino (2004) Clustering induces a lateral redistribution of alpha2beta1 integrin from membrane rafts to caveolae and subsequent protein kinase C-dependent internalization. Mol Biol Cell. 15: 625-36.

Recent review:
D.J. White, S. Puranen, M.S. Johnson, and J. Heino (2004) The collagen receptor subfamily of integrins. Int J Biochem Cell Biol. 36: 1405-10.

Host: Donald Gullberg, Department of Biomedicine

Jyrki Heino received his MD from the University of Turku, Finland, in 1984 and his MD/PhD in Medical Biochemstry from the same university in 1987. He is a leading scientist in the area of collagen receptors and has made significant contributions to the field. In the beginning of 2004, Jyrki Heino was nominated to his present position as Professor of Biochemistry at the University of Turku. He is also Scientific Director of BioCity Turku (http://www.biocity.turku.fi), one of the largest biocentres in Finland.