# Role of RILP in Autophagy

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $357,343

## Abstract

Microtubule motor proteins are responsible for numerous transport functions in cells. This proposal focuses on
a novel mechanism for the motor protein cytoplasmic dynein in mammalian autophagy. Autophagy is a critical
cellular function responsible for recycling old or damaged proteins and organelles, and for clearing toxic protein
aggregates. Autophagy is also implicated in neurodevelopmental and neurodegenerative diseases.
Cytoplasmic dynein is a major motor protein responsible for a broad range of basic cellular roles, including
retrograde axonal transport, cell division, and nuclear and cell migration. We have now found that the cytoplasmic
dynein regulator, RILP (Rab-interacting Lysosomal Protein) acts as a novel master regulator of neuronal and
nonneuronal autophagy. We find that RILP recruits dynein to autophagosomes at a succesion of stages
throughout this process via a sequence of distinct recruitment mechanisms involving interactions with the
autophagosomal proteins LC3 and ATG5, as well as the late endosomal/lysosomal protein Rab7. We find RILP
mediates not only autophagosome transport, but has a surprising role in autophagosome biogenesis as well. Of
further interest we find RILP expression to be controlled by the mTOR kinase, which plays a central role in the
cellular response to nutrient deprivation, injury, and toxic protein aggregation. We find further that RILP is
necessary for processing of p62(/SQSTM1), direct evidence for a physiological role in clearance of protein
aggregates. RILP appears, therefore, to represent a missing link in understanding how mTOR regulates the
cellular machinery in response to diverse forms of insult or stress. This proposal is to work out the detailed
mechanisms for RILP regulation and function, especially in neurons. Aim 1 will test the role of mTOR in
controlling RILP expression, and of PKA in controlling RILP/dynein-mediated autophagosome transport. Aim 2
Will define the roles of RILP in autophagosome biogenesis and maturation. Aim 3 will define the role of a novel
RILP-dynein-dynactin-LIS1 supercomplex we have isolated in regulating autophagosome transport. The
proposed studies should provide important insight into a basic new autophagy pathway, with fundamental
implications for understanding the etiology and control of neurodegenerative and neurodevelopmental diseases.

## Key facts

- **NIH application ID:** 10307619
- **Project number:** 5R01GM132478-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Richard Bert Vallee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $357,343
- **Award type:** 5
- **Project period:** 2019-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10307619

## Citation

> US National Institutes of Health, RePORTER application 10307619, Role of RILP in Autophagy (5R01GM132478-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10307619. Licensed CC0.

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