The Department of Biomedicine

CCBIO seminar: Staffan Strömblad

Novel cell-matrix adhesion structures

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Staffan Strömblad
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden

In the first part of the talk the nano-scale organization of integrins within focal adhesions will be described. Integrins fluctuate between active and inactive conformations, yet whether the activity state influences the spatial organization of integrins within focal adhesions has remained unclear. We have addressed this question and also asked whether integrin activity may be regulated independently for each integrin molecule, or through locally coordinated mechanisms. We first revealed a spatial hierarchy of integrin organization, with integrin molecules arranged in nanoclusters, which align to form linear sub-structures that in turn build focal adhesions. Remarkably, within focal adhesions, active and inactive β1 integrins segregated into distinct nanoclusters, with active integrin nanoclusters being more organized.

In the second part of the talk a novel type of adhesions will be described. Adhesion to the extracellular matrix (ECM) persists during mitosis in most cell types. However, while classical adhesion complexes, such as focal adhesions, do and must disassemble to enable mitotic rounding, the mechanisms of residual mitotic cell-ECM adhesion remain undefined. We have identified ‘reticular adhesions’, a novel class of adhesion complex that is mediated by integrin avb5, formed during interphase, and preserved at cell-ECM attachment sites throughout cell division. Mass spectrometry defined their unique composition, enriched in phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2)-binding proteins, but lacking virtually all consensus adhesome components. Indeed, reticular adhesions are promoted by PI-4,5-P2, and form independently of talin and F-actin. The distinct characteristics of reticular adhesions provide a solution to the problem of maintaining cell-ECM attachment during mitotic rounding and division.

Selected references:

Spiess M, Hernandez-Varas P, Oddone A, Olofsson H, Blom H, Waithe D, Lock JG, Lakadamyali M, Strömblad S. Active and inactive b1 integrins segregate into distinct nanoclusters in focal adhesions. J Cell Biol. 217:1929-40 (2018).

Lock JG, Jones MC, Askari JA, Gong X, Oddone A, Olofsson H, Göransson S, Lakadamyali M, Humphries MJ, Strömblad S. Reticular adhesions: A new class of adhesion complex that mediates cell-matrix attachment during mitosis. Nat Cell Biol, in press (2018).
An early version is available at: https://www.biorxiv.org/content/early/2017/12/14/234237

Chairperson: Donald Gullberg, CCBIO