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Activation of the Lysosome‐Associated p61Hck Isoform Triggers the Biogenesis of Podosomes
Author(s) -
Cougoule Céline,
Carréno Sébastien,
Castandet Jerôme,
Labrousse Arnaud,
AstarieDequeker Catherine,
Poincloux Renaud,
Le Cabec Véronique,
MaridonneauParini Isabelle
Publication year - 2005
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2005.00307.x
Subject(s) - podosome , microbiology and biotechnology , biology , invadopodia , actin , proto oncogene tyrosine protein kinase src , biogenesis , endosome , kinase , cytoskeleton , biochemistry , cell , intracellular , genetics , cancer , cancer cell , gene
Haematopoietic cell kinase (Hck) is a protein tyrosine kinase of the Src family specifically expressed in phagocytes as two isoforms, p59Hck and p61Hck, present at the plasma membrane and lysosomes, respectively. We report that ectopic expression of a constitutively active mutant of p61Hck (p61Hck ca ) triggered the de novo formation of actin‐rich rings at the ventral face of the cells that we characterized as bona fide podosome rosettes, structures involved in cell migration. Their formation required the adaptor domains and the kinase activity of p61Hck, the integrity of microfilament and microtubule networks and concerted action of Cdc42, Rac and Rho. Podosome rosette formation was either abolished when p61Hck ca was readdressed from lysosomes to the cytosol or triggered when p59Hck ca was relocalized to lysosomes. Lysosomal markers were present at podosome rosettes. By stimulating exocytosis of p61Hck ca lysosomes with a calcium ionophore, the formation of podosome rosettes was enhanced. Interestingly, we confirm that, in human macrophages, Hck and lysosomal markers were present at podosomes which were spatially reorganized as clusters, a foregoing step to form rosettes, upon expression of p61Hck ca . We propose that lysosomes, under the control of p61Hck, are involved in the biogenesis of podosomes, a key phenomenon in the migration of phagocytes.