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Molecular and Cellular Biology, September 2003, p. 6494-6506, Vol. 23, No. 18
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.18.6494-6506.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Phagosomes Fuse with Late Endosomes and/or Lysosomes by Extension of Membrane Protrusions along Microtubules: Role of Rab7 and RILP

Rene E. Harrison,1 Cecilia Bucci,2 Otilia V. Vieira,1 Trina A. Schroer,3 and Sergio Grinstein1*

Division of Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8,1 Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Universita degli Studi di Lecce, Lecce, Italy 73100,2 Department of Biology, The Johns Hopkins University, Baltimore, Maryland 212183

Received 19 February 2003/ Returned for modification 8 May 2003/ Accepted 25 June 2003

Nascent phagosomes must undergo a series of fusion and fission reactions to acquire the microbicidal properties required for the innate immune response. Here we demonstrate that this maturation process involves the GTPase Rab7. Rab7 recruitment to phagosomes was found to precede and to be essential for their fusion with late endosomes and/or lysosomes. Active Rab7 on the phagosomal membrane associates with the effector protein RILP (Rab7-interacting lysosomal protein), which in turn bridges phagosomes with dynein-dynactin, a microtubule-associated motor complex. The motors not only displace phagosomes in the centripetal direction but, strikingly, promote the extension of phagosomal tubules toward late endocytic compartments. Fusion of tubules with these organelles was documented by fluorescence and electron microscopy. Tubule extension and fusion with late endosomes and/or lysosomes were prevented by expression of a truncated form of RILP lacking the dynein-dynactin-recruiting domain. We conclude that full maturation of phagosomes requires the retrograde emission of tubular extensions, which are generated by activation of Rab7, recruitment of RILP, and consequent association of phagosomes with microtubule-associated motors.

* Corresponding author. Mailing address: Programme in Cell Biology, Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8. Phone: (416) 813-5727. Fax: (416) 813-5028. E-mail: sga{at}sickkids.ca.

Molecular and Cellular Biology, September 2003, p. 6494-6506, Vol. 23, No. 18
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.18.6494-6506.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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