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Vol. 20, Issue 6, 1878-1889, March 15, 2009

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Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

Instituto de Investigaciones Biotecnológicas, Universidad de San Martín, 1650 San Martín, Buenos Aires, Argentina

Submitted July 2, 2008; Revised December 15, 2008; Accepted January 13, 2009
Monitoring Editor: Erika L. Holzbaur

PTP1B is an ER-bound protein tyrosine phosphatase implied in the regulation of cell adhesion. Here we investigated mechanisms involved in the positioning and dynamics of PTP1B in axonal growth cones and evaluated the role of this enzyme in axons. In growth cones, PTP1B consistently localizes in the central domain, and occasionally at the peripheral region and filopodia. Live imaging of GFP-PTP1B reveals dynamic excursions of fingerlike processes within the peripheral region and filopodia. PTP1B and GFP-PTP1B colocalize with ER markers and coalign with microtubules at the peripheral region and redistribute to the base of the growth cone after treatment with nocodazole, a condition that is reversible. Growth cone contact with cellular targets is accompanied by invasion of PTP1B and stable microtubules in the peripheral region aligned with the contact axis. Functional impairment of PTP1B causes retardation of axon elongation, as well as reduction of growth cone filopodia lifetime and Src activity. Our results highlight the role of microtubules and cell contacts in the positioning of ER-bound PTP1B to the peripheral region of growth cones, which may be required for the positive role of PTP1B in axon elongation, filopodia stabilization, and Src activity.

Address correspondence to: Carlos O. Arregui (carregui{at}iib.unsam.edu.ar)

Abbreviations used: BIFC, bimolecular fluorescence complementation; BRET, bioluminiscence resonance energy transfer; FRET, fluorescence resonance energy transfer; RGC, retinal ganglion cell.