The epithelial sodium channel mediates the directionality of galvanotaxis in human keratinocytes

Yang, Hsin-Ya; Charles, Roch-Philippe; Hummler, Edith; Baines, Deborah L.; Isseroff, R. Rivkah (2013). The epithelial sodium channel mediates the directionality of galvanotaxis in human keratinocytes. Journal of cell science, 126(Pt 9), pp. 1942-1951. Company of Biologists Limited 10.1242/jcs.113225

[img] Text
1942.full.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (3MB) | Request a copy

Cellular directional migration in an electric field (galvanotaxis) is one of the mechanisms guiding cell movement in embryogenesis and in skin epidermal repair. The epithelial sodium channel (ENaC), in addition to its function of regulating sodium transport in kidney, has recently been found to modulate cell locomotory speed. Here we tested whether ENaC has an additional function of mediating the directional migration of galvanotaxis in keratinocytes. Genetic depletion of ENaC completely blocks only galvanotaxis and does not decrease migration speed. Overexpression of ENaC is sufficient to drive galvanotaxis in otherwise unresponsive cells. Pharmacologic blockade or maintenance of the open state of ENaC also decreases or increases, respectively, galvanotaxis, suggesting that the channel open state is responsible for the response. Stable lamellipodial extensions formed at the cathodal sides of wild-type cells at the start of galvanotaxis; these were absent in the ENaC knockout keratinocytes, suggesting that ENaC mediates galvanotaxis by generating stable lamellipodia that steer cell migration. We provide evidence that ENaC is required for directional migration of keratinocytes in an electric field, supporting a role for ENaC in skin wound healing.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Charles, Roch-Philippe

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0021-9533

Publisher:

Company of Biologists Limited

Language:

English

Submitter:

Roch-Philippe Charles

Date Deposited:

25 Feb 2014 10:48

Last Modified:

11 Nov 2015 13:41

Publisher DOI:

10.1242/jcs.113225

PubMed ID:

23447677

Uncontrolled Keywords:

Directional migration, ENaC, Keratinocyte, Lamellipodia

BORIS DOI:

10.7892/boris.41289

URI:

https://boris.unibe.ch/id/eprint/41289

Actions (login required)

Edit item Edit item
Provide Feedback