Rab5 mediates caspase-8-promoted cell motility and metastasis.

Molecular Biology of the Cell
Vicente A TorresD G Stupack

Abstract

Caspase-8 is a key apical sensory protein that governs cell responses to environmental cues, alternatively promoting apoptosis, proliferation, and cell migration. The proteins responsible for integration of these pathways, however, have remained elusive. Here, we reveal that Rab5 regulates caspase-8-dependent signaling from integrins. Integrin ligation leads to Rab5 activation, association with integrins, and activation of Rac, in a caspase-8-dependent manner. Rab5 activation promotes colocalization and coprecipitation of integrins with caspase-8, concomitant with Rab5 recruitment to integrin-rich regions such as focal adhesions and membrane ruffles. Moreover, caspase-8 expression promotes Rab5-mediated internalization and the recycling of beta1 integrins, increasing cell migration independently of caspase catalytic activity. Conversely, Rab5 knockdown prevented caspase-8-mediated integrin signaling for Rac activation, cell migration, and apoptotic signaling, respectively. Similarly, Rab5 was critical for caspase-8-driven cell migration in vivo, because knockdown of Rab5 compromised the ability of caspase-8 to promote metastasis under nonapoptotic conditions. These studies identify Rab5 as a key integrator of caspase-8-mediated...Continue Reading

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Citations

Oct 28, 2010·Journal of Proteome Research·Karen S AndersonJoshua Labaer
Jul 23, 2014·The Journal of Cell Biology·Emanuela FrittoliGiorgio Scita
Oct 1, 2014·Communicative & Integrative Biology·Jorge DíazVicente A Torres
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Methods Mentioned

BETA
GTPases
electrophoresis
pull-down
Assay
flow cytometry
GTPase
confocal microscopy
immunoprecipitation
fluorescence-activated cell sorting
fluorescence microscopy

Software Mentioned

Image J
NIH
GraphPad
ImageJ
Photoshop
CellQuest
InStat

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