title: S100A4 downregulates filopodia formation through increased dynamic instability.
abstract: Cell migration requires the initial formation of cell protrusions, lamellipodia and/or filopodia, the attachment of the leading lamella to extracellular cues and the formation and efficient recycling of focal contacts at the leading edge. The small calcium binding EF-hand protein S100A4 has been shown to promote cell motility but the direct molecular mechanisms responsible remain to be elucidated. In this work, we provide new evidences indicating that elevated levels of S100A4 affect the stability of filopodia and prevent the maturation of focal complexes. Increasing the levels of S100A4 in a rat mammary benign tumor derived cell line results in acquired cellular migration on the wound healing scratch assay. At the cellular levels, we found that high levels of S100A4 induce the formation of many nascent filopodia, but that only a very small and limited number of those can stably adhere and mature, as opposed to control cells, which generate fewer protrusions but are able to maintain these into more mature projections. This observation was paralleled by the fact that S100A4 overexpressing cells were unable to establish stable focal adhesions. Using different truncated forms of the S100A4 proteins that are unable to bind to myosin IIA, our data suggests that this newly identified functions of S100A4 is myosin-dependent, providing new understanding on the regulatory functions of S100A4 on cellular migration.
authors: School of Life and Health Sciences; Aston University; Birmingham, UK.
authors: Connie
authors: C
authors: Goh Then Sin
authors: Nils
authors: N
authors: Hersch
authors: Philip S
authors: PS
authors: Rudland
authors: Roger
authors: R
authors: Barraclough
authors: Bernd
authors: B
authors: Hoffmann
authors: Stephane R
authors: SR
authors: Gross
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D015536:Down-Regulation; D022001:Focal Adhesions / Q000378:metabolism*; D024507:Nonmuscle Myosin Type IIA / Q000737:chemistry / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*; D051381:Rats; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C499412:S100a4 protein, rat; D024507:Nonmuscle Myosin Type IIA