First published online December 31, 2003
Journal of Cell Science 117, 302e (2004)
© The Company of Biologists Limited
Annexin' osteoblasts
Mineralization of bone involves secretion of extracellular matrix (ECM) and associated molecules by specialized cells termed osteoblasts. Key proteins in this process include collagen I and alkaline phosphatase (ALP), which promotes mineralization by breaking down pyrophosphate. How mineralization is regulated has been unclear, but Jennifer Gillette and Sheila Nielsen-Preiss now show that annexin 2 one of a family of proteins implicated in membrane trafficking and signalling plays a part. Having picked out annexin 2 in a screen for genes expressed in bone malignancies, the authors show that its expression increases ALP activity in osteoblasts and promotes mineralization whereas antisense annexin 2 oligonucleotides inhibit this (see p. 441). Annexin 2 does not stimulate synthesis of ALP. However, Gillette and Nielsen-Preiss notice that annexin 2 and ALP both localize to lipid rafts (ordered plasma membrane microdomains) and that overexpression of annexin 2 increases raft-associated ALP activity. Furthermore, they find that cholesterol-sequestering agents that disrupt rafts reduce both mineralization and ALP activity. Annexin 2 thus appears to regulate the organization of ALP-containing lipid rafts in osteoblasts. The authors propose that it promotes their coalescence, which could activate ALP directly and/or stimulate signalling cascades that target it.

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Related articles in JCS:
- The role of annexin 2 in osteoblastic mineralization
- Jennifer M. Gillette and Sheila M. Nielsen-Preiss
JCS 2004 117: 441-449.
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