The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors.

By Ingrid Jordens, M. Fernandez-Borja, M. Marsman, S. Dusseljee, L. Janssen, J. Calafat, H. Janssen, R. Wubbolts, J. Neefjes. Current Biology, 2001

821 citations recorded by the source corpus.

Many intracellular compartments, including MHC class II-containing lysosomes, melanosomes, and phagosomes, move along microtubules in a bidirectional manner and in a stop-and-go fashion due to the alternating activities of a plus-end directed kinesin motor and a minus-end directed dynein-dynactin motor. It is largely unclear how motor proteins are targeted specifically to different compartments. Rab GTPases recruit and/or activate several proteins involved in membrane fusion and vesicular transport. They associate with specific compartments after activation, which makes Rab GTPases ideal candidates for controlling motor protein binding to specific membranes. We and others [7] have identified a protein, called RILP (for Rab7-interacting lysosomal protein), that interacts with active Rab7 on late endosomes and lysosomes. Here we show that RILP prevents further cycling of Rab7. RILP expression induces the recruitment of functional dynein-dynactin motor complexes to Rab7-containing late endosomes and lysosomes. Consequently, these compartments are transported by these motors toward the minus end of microtubules, effectively inhibiting their transport toward the cell periphery. This signaling cascade may be responsible for timed and selective dynein motor recruitment onto late endosomes and lysosomes.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/16fda2634aecca4ba1085db93313e27979f40f52

How researchers see this paper

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In Cell Biology

1. Ari Helenius
2. Jatta Huotari
3. Harald A. Stenmark
4. P. Saftig
5. E. Holzbaur
6. J. Colicelli
7. E. Eskelinen
8. Alison E. Twelvetrees

In Molecular Biology

1. E. Holzbaur
2. Ari Helenius
3. Jatta Huotari
4. P. Saftig
5. Harald A. Stenmark
6. J. Colicelli
7. E. Eskelinen
8. Alison E. Twelvetrees

Citations in the corpus

• Macrophage defense mechanisms against intracellular bacteria (2015, background): “Downstream effector proteins of Rab7A include the Rab-interacting lysosomal protein (RILP), which links the phagosomal membrane to a motor complex consisting of dynein and dynactin through stepwise recruitment of p150Glued, ORP1L, and the receptor blll spectrin (33, 34).”
• Antimicrobial mechanisms of phagocytes and bacterial evasion strategies (2009, background): “One such effector, Rab-interacting lysosomal protein ( RILP ), promotes the centripetal movement of late phagosomes and lysosomes by bridging the membrane to the dynein–dynactin motor complex proces”
• AXONAL TRANSPORT: CARGO-SPECIFIC MECHANISMS OF MOTILITY AND REGULATION (2014, background): “Dynein is recruited to late endosomes and lysosomes via the Rab7 effector RILP (Rab7-interacting lysosomal protein), which interacts directly with the C terminus of the p150Glued subunit of dynactin (Johansson et al., 2007; Jordens et al., 2001).”
• Human RAS Superfamily Proteins and Related GTPases (2004, background): “The participation of RAB7 in lysosomal transport has been attributed in part to the effector protein RILP (Rab7-interacting lysosomal protein) (220, 221).”
• Rab GTPases as coordinators of vesicle traffic (2009, background): “The RAB7 effector Rab-interacting lysosomal protein (RILP) mediates minus-end-directed trafficking of late endosomes by recruiting a subunit of the dynactin complex, which is associated with dynei”
• Lysosomes: fusion and function (2007, background): “Such movement is mediated by motor proteins and proteins that are required for the optimal attachment of these motors to late endocytic organelles, including the RAB7 effector RAB7-interacting lysosomal protein (RILP”
• Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. (2010, neutral): “RILP and ORP1L have been identified as dynactin complexbinding proteins (Johansson et al., 2007; Jordens et al., 2001).”
• Endosome maturation (2011, background): “Although more prominently known for its role in establishing contact with dynactin/dynein motors and thereby regulating LE motility (Jordens et al, 2001; Johansson et al, 2007), RILP may have additional Rab7-independent functions.”
• LAMP proteins are required for fusion of lysosomes with phagosomes (2007, background): “Dynein, which mediates retrograde movement of lysosomes along microtubules (Jordens et al, 2001), is thought to predominate over kinesin(s), which are responsible for anterograde transport (Hollenbeck and Swanson, 1990).”