Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Nerve cell response to external cues is vital for neural circuit formation and maintenance.
• Adaptor molecules are essential for activating specific downstream pathways in neurons.

Purpose of the Study:

• To investigate the role of DOK6 (downstream of tyrosine kinases 6) in the maintenance of peripheral axons.
• To elucidate the molecular mechanisms by which DOK6 influences axonal transport and survival.

Main Methods:

• Genetic deletion of Dok6 in peripheral neurons of mice.
• Analysis of peripheral neuropathy symptoms, including sensory function, posture, and nerve conduction.
• Investigation of DOK6 interactions with trafficking machinery and downstream signaling pathways like ERK1/2.

Main Results:

• Loss of Dok6 in mice leads to peripheral neuropathy symptoms: impaired sensory function, abnormal posture, paw deformities, blocked nerve conduction, and dysmyelination.
• Dok6 deletion in peripheral neurons causes myelin outfolding, axon destruction, and impaired retrograde axonal transport.
• DOK6 functions as an adaptor protein for TrkC and Ret signaling, interacting with MAP1B, Tau, and Dynein to regulate axonal transport and activating ERK1/2 for axonal survival.

Conclusions:

• DOK6 is essential for the maintenance of peripheral axons and normal nerve function.
• DOK6 plays a critical role in neurotrophic signal transduction and retrograde axonal transport.
• Understanding DOK6's function offers insights into the pathogenesis of peripheral neuropathies and degenerative diseases.