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Lipid modification in Wnt structure and function

Ke, Jiyuana; Xu, H. Erica; Williams, Bart O.b

Current Opinion in Lipidology: April 2013 - Volume 24 - Issue 2 - p 129–133
doi: 10.1097/MOL.0b013e32835df2bf
GENETICS AND MOLECULAR BIOLOGY: Edited by Robert Hegele

Purpose of review: Wnt proteins are morphogens encoded by 19 mammalian genes that play essential roles in embryonic development, stem cell renewal, and adult tissue homeostasis. The recent publication of the first crystal structure of a Wnt protein represents a key step in the study of Wnt signaling.

Recent findings: We discuss the basic aspects of Wnt signaling, provide historical background for why the proteins have been so challenging to study from a biochemical perspective, describe the lipid modifications that occur to Wnt proteins, and then discuss the implications of the recently reported crystal structure.

Summary: The recent determination of the Wnt8-Fz8 structure has created new opportunities to better understand the mechanisms by which Wnt proteins activate downstream signaling pathways and has further clarified why lipid modification of Wnt is required for activation.

aLaboratory of Structural Studies

bCenter for Skeletal Disease Research, Van Andel Research Institute, Grand Rapids, Michigan, USA

Correspondence to Bart O. Williams, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USA. Tel: +1 616 234 5308; fax: +1 616 234 5309; e-mail: bart.williams@vai.org

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins