Neurons dispose of hyperactive kinesin into glial cells for clearance

Area of Science:

• Cell Biology
• Neuroscience
• Molecular Motors

Background:

• Microtubule-based kinesin motor proteins are essential for intracellular transport.
• Hyperactivation of kinesin motors can disrupt cellular functions and lead to disease.
• Understanding mechanisms that regulate kinesin activity is crucial for cellular health.

Purpose of the Study:

• To investigate the cellular fate of a constitutively active ciliary kinesin mutant, OSM-3CA, in C. elegans sensory cilia.
• To identify genetic factors and cellular processes involved in regulating hyperactive kinesin motor proteins.

Main Methods:

• Utilized C. elegans as a model organism to study sensory cilia.
• Generated and analyzed a constitutively active kinesin mutant (OSM-3CA).
• Employed genetic suppressor screens to identify mutations affecting OSM-3CA localization and function.
• Investigated cellular engulfment pathways involving the CED-1 receptor.

Main Results:

• OSM-3CA was unexpectedly absent from cilia and was disposed of via membrane abscission at aberrant neurite tips.
• Neighboring glial cells engulfed and eliminated OSM-3CA, dependent on the CED-1 receptor.
• Suppressor mutations in the OSM-3CA motor domain or the ciliary kinase DYF-5 restored normal cilia.
• Conformational changes in OSM-3CA and its hyperactivity were critical for its disposal.
• Evidence suggests neurons also dispose of hyperactive kinesin-1 associated with amyotrophic lateral sclerosis.

Conclusions:

• Cells possess a mechanism to eliminate hyperactive kinesin motor proteins through membrane abscission and glial engulfment.
• This disposal process is essential for maintaining cellular function and preventing pathology.
• The findings suggest a conserved mechanism for regulating kinesin activity across different cell types and in disease contexts.