Expected and unexpected roles for dynein regulation of dendritic late endosomes

Abstract

Dendrites differ from axons in multiple ways, including the presence of minus-end out microtubules intermixed with the more conventional plus-end out microtubules. The mixed microtubule polarity makes regulation of directional transport in dendrites a challenge. Dynein can in principle be a retrograde and anterograde motor in dendrites. We show in our recent paper that dynein supports bi-directional transport of late endosomes in dendrites. We also show that overexpression of the RAB7 effector RILP which recruits dynein to late endosomes imparts retrograde bias onto late endosomes. Inhibition of dynein leads to a decrease in bi-directional motility of late endosomes, an expected result. Unexpectedly, inhibition of dynein also impairs endosome maturation as evidenced by increased association of GTP-RAB7 with late endosomes. Ultimately, dynein inhibition causes degradation defects of short-lived dendritic receptors and stunted dendrite morphologies. Much more work is required to fully understand how endosomal pathways are regulated in time and space in dendrites. Given the prevalence of neurological disorders where endosome-lysosome functions are impaired, this is a topic of great translational relevance. Abbreviations: RILP: Rab-interacting lysosomal protein; EE: early endosome; LE: late endosome; lys: lysosome; NSG2: neural-specific gene 2; RILP-CT: RILP C-terminal truncation.

Keywords

• degradation
• dendrite
• dynein
• late endosome
• lysosome
• maturation
• neuron
• nsg2
• rab7
• rilp