Late endosome transport by RILP-RAB7A promotes dendrite arborization.

Area of Science:

• Cell Biology
• Neuroscience
• Molecular Biology

Background:

• Retrograde transport of late endosomes (LEs) to the soma is crucial for lysosomal fusion and degradation.
• Dendritic LE motility and somatic degradation depend on RAB7A and dynein.
• RAB7A and dynein are linked by RILP, a RAB7A effector that also interacts with the HOPS complex.

Purpose of the Study:

• To investigate the role of the RAB7A-RILP interaction in neuronal endosome transport, degradation, and dendrite morphology.
• To test the hypothesis that neuronal endosome motility and degradation depend on RILP, based on non-neuronal cell studies.

Main Methods:

• Expression of a separation-of-function RAB7A mutant (RAB7A-L8A) that cannot bind RILP in cultured rat and mouse hippocampal neurons.
• Analysis of late endosome motility, lysosomal fusion, cargo degradation, and dendrite arborization in neurons expressing RAB7A-L8A.

Main Results:

• Endogenous RILP acts as a RAB7A-dependent dynein adaptor for LE motility in dendrites, promoting endosome carrier formation.
• Inhibition of LE transport by RAB7A-L8A expression leads to impaired clearance of degradative cargo from dendrites.
• Lysosomal fusion and somatic degradation remain normal, indicating RAB7A-RILP interaction is not required for these processes.
• Dendrite arborization is impaired in RAB7A-L8A expressing neurons, despite normal degradation, separating morphology defects from degradation blockade.

Conclusions:

• Neuronal dendrite growth and maintenance depend on RAB7A/RILP-mediated late endosome transport.
• The RAB7A-RILP interaction is essential for LE motility and cargo clearance in dendrites but not for lysosomal fusion or somatic degradation.
• Dendrite morphology defects are separable from degradation blockade, highlighting a distinct role for LE transport in neuronal development.