Locomotion guidance by extracellular matrix is adaptive and can be restored by a transient change in Ca2+ level

Hong Wen Liu*, Yun Cin Luo, Chia Lin Ho, Jung Yen Yang, Chi Hung Lin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Navigation of cell locomotion by gradients of soluble factors can be desensitized if the concentration of the chemo-attractant stays unchanged. It remains obscure if the guidance by immobilized extracellular matrix (ECM) as the substrate is also adaptive and if so, how can the desensitized ECM guidance be resensitized. When first interacting with a substrate containing micron-scale fibronectin (FBN) trails, highly motile fish keratocytes selectively adhere and migrate along the FBN paths. However, such guided motion become adaptive after about 10 min and the cells start to migrate out of the ECM trails. We found that a burst increase of intracellular calcium created by an uncaging technique immediately halts the undirected migration by disrupting the ECM-cytoskeleton coupling, as evidenced by the appearance of retrograde F-actin flow. When the motility later resumes, the activated integrin receptors render the cell selectively binding to the FBN path and reinitiates signaling events, including tyrosine phosphorylation of paxillin, that couple retrograde F-actin flow to the substrate. Thus, the calcium-resensitized cell can undergo a period of ECM-navigated movement, which later becomes desensitized. Our results also suggest that endogenous calcium transients as occur during spontaneous calcium oscillations may exert a cycling resensitization-desensitization control over cell's sensing of substrate guiding cues.

Original languageEnglish
Article numbere7330
JournalPLoS ONE
Issue number10
StatePublished - 5 Oct 2009

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