5x57 | pdb_00005x57
Structure of GAR domain of ACF7
Structural highlights
Function[MACF1_HUMAN] Isoform 2 is a F-actin-binding protein which may play a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane. Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics. May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4. Plays a key role in wound healing and epidermal cell migration. Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate MT dynamics and polarize hair follicle stem cells (By similarity).[1] [2] Publication Abstract from PubMedIn the intestinal epithelium, the aberrant regulation of cell/cell junctions leads to intestinal barrier defects, which may promote the onset and enhance the severity of inflammatory bowel disease (IBD). However, it remains unclear how the coordinated behaviour of cytoskeletal network may contribute to cell junctional dynamics. In this report, we identified ACF7, a crosslinker of microtubules and F-actin, as an essential player in this process. Loss of ACF7 leads to aberrant microtubule organization, tight junction stabilization and impaired wound closure in vitro. With the mouse genetics approach, we show that ablation of ACF7 inhibits intestinal wound healing and greatly increases susceptibility to experimental colitis in mice. ACF7 level is also correlated with development and progression of ulcerative colitis (UC) in human patients. Together, our results reveal an important molecular mechanism whereby coordinated cytoskeletal dynamics contributes to cell adhesion regulation during intestinal wound repair and the development of IBD. ACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics.,Ma Y, Yue J, Zhang Y, Shi C, Odenwald M, Liang WG, Wei Q, Goel A, Gou X, Zhang J, Chen SY, Tang WJ, Turner JR, Yang F, Liang H, Qin H, Wu X Nat Commun. 2017 May 25;8:15375. doi: 10.1038/ncomms15375. PMID:28541346[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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