Dendrites use mechanosensitive channels to proofread ligand-mediated neurite extension during morphogenesis

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• Ligand-receptor interactions and mechanical forces guide neuronal development.
• The precise mechanisms of mechanical force sensing and their integration with guidance receptors remain unclear.

Purpose of the Study:

• To investigate the role of mechanosensitive channels in dendritic arbor morphogenesis.
• To identify the specific mechanosensors involved and their interaction with guidance receptors.

Main Methods:

• Utilized Caenorhabditis elegans as a model organism.
• Inhibited DEG/ENaC channels and overexpressed PEZO-1/Piezo and YVC1/TrpY1 channels.
• Analyzed dendritic outgrowth and branching in vivo.
• Investigated calcium transients in dendritic filopodia using live imaging.

Main Results:

• Inhibition of DEG/ENaC channels led to reduced dendritic outgrowth and branching.
• Overexpression of PEZO-1/Piezo or YVC1/TrpY1 alleviated these defects.
• DEG/ENaCs activated local calcium transients via L-type voltage-gated calcium channels.
• Mechanical activation of DEG/ENaC channels required filopodia anchoring by ligand-receptor complexes.

Conclusions:

• Mechanosensitive DEG/ENaC channels are essential for dendritic arbor morphogenesis.
• These channels act as a checkpoint for chemoaffinity, regulating calcium transients necessary for neurite growth.