Microtubule plus-end tracking protein CLASP2 regulates neuronal polarity and synaptic function

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Microtubule dynamics are crucial for neuronal development, including axon and dendrite formation.
• Regulation of microtubule dynamics during synaptic development in mammals remains poorly understood.

Purpose of the Study:

• To investigate the role of CLASP2 (cytoplasmic linker associated protein 2) in neuronal morphogenesis and synaptic function.
• To elucidate the mechanisms by which CLASP2 influences microtubule organization and synaptic activity.

Main Methods:

• Utilized short-hairpin RNA (shRNA) to knockdown CLASP2 in primary mouse neurons.
• Overexpressed human CLASP2 in primary mouse neurons.
• Analyzed neuronal morphology, synaptic transmission, and protein localization using various imaging and biochemical techniques.

Main Results:

• CLASP2 knockdown reduced axon and dendritic length.
• CLASP2 overexpression promoted increased axon and dendrite outgrowth, enhanced branching, and Golgi condensation.
• CLASP2 overexpression significantly increased spontaneous miniature event frequency, presynaptic terminal size, synapse number, and presynaptic protein levels, alongside a smaller increase in miniature event amplitude and postsynaptic GluA1 receptor localization.

Conclusions:

• CLASP2 is a key regulator of neuronal polarity and morphogenesis.
• CLASP2 influences synapse formation and function by modulating microtubule stabilization.
• Findings highlight the interplay between microtubule dynamics and synaptic development in mammalian neurons.