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Armus is a Rac1 effector that inactivates Rab7 and regulates E-cadherin degradation.

Frasa, MA, Maximiano, FC, Smolarczyk, K, Francis, RE, Betson, ME, Lozano, E, Goldenring, J, Seabra, MC, Rak, A, Ahmadian, MR and Braga, VM (2010) Armus is a Rac1 effector that inactivates Rab7 and regulates E-cadherin degradation. Curr Biol, 20 (3). pp. 198-208.

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Abstract

BACKGROUND: Cell-cell adhesion and intracellular trafficking are regulated by signaling pathways from small GTPases of the Rho, Arf, and Rab subfamilies. How signaling from distinct small GTPases are integrated in a given process is poorly understood. RESULTS: We find that a TBC/RabGAP protein, Armus, integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Armus binds specifically to activated Rac1 and its C-terminal TBC/RabGAP domain inactivates Rab7. Thus, Armus is a novel Rac1 effector and a bona fide GAP for Rab7 in vitro and in vivo, a unique and previously unreported combination. Arf6 activation efficiently disrupts cell-cell contacts and is known to activate Rac1 and Rab7. Arf6-induced E-cadherin degradation is efficiently blocked by expression of Armus C-terminal domain or after Armus RNAi. Coexpression of Arf6 with dominant-negative Rab7 or Rac1 also inhibits junction disassembly. Importantly, Armus RabGAP expression also prevents EGF-induced scattering in keratinocytes, a process shown here to require Arf6, Rac1, and Rab7 function. To our knowledge, this is the first report to demonstrate a molecular and functional link between Rac1 and Rab7. CONCLUSIONS: Our data indicate that active Rac1 recruits Armus to locally inactivate Rab7 and facilitate E-cadherin degradation in lysosomes. Thus, the integration of Rac1 and Rab7 activities by Armus provides an important regulatory node for E-cadherin turnover and stability of cell-cell contacts.

Item Type: Article
Authors :
NameEmailORCID
Frasa, MAUNSPECIFIEDUNSPECIFIED
Maximiano, FCUNSPECIFIEDUNSPECIFIED
Smolarczyk, KUNSPECIFIEDUNSPECIFIED
Francis, REUNSPECIFIEDUNSPECIFIED
Betson, MEm.betson@surrey.ac.ukUNSPECIFIED
Lozano, EUNSPECIFIEDUNSPECIFIED
Goldenring, JUNSPECIFIEDUNSPECIFIED
Seabra, MCUNSPECIFIEDUNSPECIFIED
Rak, AUNSPECIFIEDUNSPECIFIED
Ahmadian, MRUNSPECIFIEDUNSPECIFIED
Braga, VMUNSPECIFIEDUNSPECIFIED
Date : 9 February 2010
Identification Number : https://doi.org/10.1016/j.cub.2009.12.053
Uncontrolled Keywords : Animals, COS Cells, Cadherins, Carrier Proteins, Cell Communication, Cells, Cultured, Cercopithecus aethiops, GTPase-Activating Proteins, Humans, Intercellular Junctions, Keratinocytes, Models, Biological, Recombinant Proteins, Signal Transduction, rab GTP-Binding Proteins, rac1 GTP-Binding Protein
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:33
Last Modified : 17 May 2017 14:50
URI: http://epubs.surrey.ac.uk/id/eprint/828289

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