Subject: MP to consider
Date: Wed, 28 Oct 2009 18:17:05 -0400
From: Melissa Berry <Melissa.Berry@jax.org>
To: Cynthia Smith <email@example.com>
(really, I didn’t make that up)
Hmm- do we want to add this or keep podosome pheontypes annotated to the particular cell type they are associated with?
from: PMID: 18606851
Podosomes (also termed invadopodia in cancer cells) are actin-rich adhesion structures with matrix degradation activity that develop in various cell types. Despite their significant physiological importance, the molecular mechanism of podosome formation is largely unknown.
Podosomes/invadopodia are cellular appendages that are formed on the ventral surface of the plasma membrane perpendicular to and in contact with the extracellular matrix (ECM). They appear to be involved in a wide range of physiological and pathological aspects such as sealing-ring formation in osteoclasts (Destaing et al., 2003; Jurdic et al., 2006), transcellular diapedesis of leukocytes (Carman et al., 2007), and invasion of cancer cells into the ECM (Yamaguchi et al., 2006).
They comprise dot-shaped, F-actin–rich contact regions that appear as small (diameter of 1–2 µm and depth of 200–400 nm) plasma membrane extensions when observed under an electron microscope; they assemble at an early stage during cell adhesion to a substrate. They are enriched with adhesion molecules, actin-modulating proteins, tyrosine kinases, matrix proteases, and tyrosine-phosphorylated proteins (David-Pfeuty and Singer, 1980; Tarone et al., 1985; Marchisio et al., 1988; Buccione et al., 2004; Gimona, 2008). Among them, the Arp2/3 complex and its activators Wiskott-Aldrich syndrome protein (WASP) or N-WASP in nonhematopoietic cells are the primary machinery for the assembly of F-actin columns in various cell types (Mizutani et al., 2002; Yamaguchi et al., 2005; Olivier et al., 2006). Upstream regulators of N-WASP including Cdc42, Nck1, and WIP, have also been proved to be essential for EGF-induced invadopodia formation in mammary carcinoma cells (Yamaguchi et al., 2005), thereby confirming the importance of this molecule. However, the precise pathways regarding the spatio-temporal orchestration leading to WASP/N-WASP–induced actin polymerization is largely unknown.
abnormal podosome formation (assembly/disassembly?)
Podosome phenotypes should remain with the cell type they are associated with.