Phosphorylation enables progressive microtubule-associated protein proteolysis and functionalisation during neural...

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Microtubule cytoskeleton is vital for neuronal function and integrity.
• Dysregulation of microtubules is common in neurological diseases.
• Mechanisms regulating microtubule dynamics during neurodevelopment are poorly understood.

Purpose of the Study:

• Identify cytoskeletal substrates of Ser-Arg Protein Kinase (SRPK).
• Investigate the role of SRPK in regulating Microtubule Associated Protein 1S (MAP1S) during neurodevelopment.
• Elucidate the functional consequences of MAP1S phosphorylation and processing.

Main Methods:

• Global phosphoproteomic screening to identify SRPK substrates.
• In vitro phosphorylation assays to confirm SRPK-MAP1S interaction.
• Analysis of MAP1S proteolytic processing by Calpain 10 (CAPN10).
• Assessment of MAP1S microtubule binding affinity.

Main Results:

• SRPK directly phosphorylates MAP1S at multiple sites.
• SRPK-dependent phosphorylation modulates MAP1S microtubule binding and proteolytic processing by CAPN10.
• MAP1S processing occurs progressively during neurodevelopment, linked to CAPN10 expression.
• MAP1S acquires microtubule binding activity post-processing.

Conclusions:

• SRPK coordinates MAP1S processing and functionalization during neurodevelopment.
• This pathway is critical for microtubule regulation in neurons.
• Findings provide insights into microtubule cytoskeleton dysregulation in neurological diseases.