Late Endosome Transport by RILP-RAB7A Promotes Dendrite Arborization Independently of Degradation

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Directional transport of late endosomes (LEs) to the soma is crucial for lysosomal fusion and degradation.
• RAB7A and dynein motor proteins are essential for LE motility and neuronal function.
• RILP acts as a linker between RAB7A, dynein, and the HOPS complex, mediating LE-lysosome fusion.

Purpose of the Study:

• To investigate the role of the RAB7A-RILP interaction in neuronal late endosome transport and dendrite growth.
• To determine if RILP is essential for RAB7A-dependent dynein-mediated LE motility in dendrites.
• To elucidate the specific contributions of LE transport and degradation to dendrite morphology.

Main Methods:

• Utilized a separation-of-function RAB7A mutant (RAB7A-L8A) that cannot bind RILP in cultured rat and mouse hippocampal neurons.
• Assessed LE motility, endosome carrier formation, and cargo clearance in neurons expressing RAB7A-L8A.
• Evaluated lysosomal fusion, somatic degradation, and dendrite arborization in experimental conditions.

Main Results:

• Endogenous RILP functions as a RAB7A-dependent dynein adaptor, promoting LE motility and carrier formation in dendrites.
• Impaired LE transport in RAB7A-L8A neurons leads to accumulation of degradative cargo in dendrites.
• Lysosomal fusion and somatic degradation are surprisingly independent of the RAB7A-RILP interaction.
• Dendrite arborization is impaired in RAB7A-L8A neurons, despite normal degradation, indicating a role for RAB7A/RILP-dependent transport in dendrite growth.

Conclusions:

• Neuronal dendrite growth and maintenance depend on RAB7A/RILP-mediated late endosome transport.
• This transport function is separable from the role of LEs in cargo degradation.
• The RAB7A-RILP pathway is critical for supporting dendrite development independently of lysosomal degradation pathways.