PAK4 and αPIX determine podosome size and number in macrophages through localized actin regulation

Alexandra Gringel, Daniel Walz, Georg Rosenberger, Audrey Minden, Kerstin Kutsche, Petra Kopp, Stefan Linder

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Podosomes are actin-rich adhesion structures typical for monocytic cells and are implicated in migration and invasion. Major modes of podosome regulation include RhoGTPase signaling and actin regulatory pathways. However, it is not clearly understood how these signals induce highly localized changes in podosome formation and dynamics. Here, we show that the RhoGTPase effector PAK4, a member of the p21 associated kinase family, and its regulator αPIX (PAK-interacting exchange factor), are central to podosome formation in primary human macrophages. Immunofluorescence, biochemical and microarray data indicate that PAK4 acts as physiological regulator of podosomes in this system. Accordingly, transfection of a specific shRNA, as well as expression of PAK4 truncation mutants, resulted in reduced numbers of podosomes per cell. Moreover, expression of kinase active or inactive PAK4 mutants enhanced or reduced the size of individual podosomes, respectively, indicating a modulatory influence of PAK4 kinase activity on podosome size. Similar to the results gained with PAK4, cellular/overexpressed PIX was shown to be closely associated with podosomes. Moreover, both overexpression of αPIX wt and a mutant lacking the SH3 domain led to coalescence of podosomes. In sum, we propose that PAK4 and αPIX can induce highly localized changes in actin dynamics and thereby regulate size and number of podosomes in primary human macrophages.

Original languageEnglish (US)
Pages (from-to)568-579
Number of pages12
JournalJournal of Cellular Physiology
Issue number2
StatePublished - Nov 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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