Rab8a/Rab11a regulate intercellular communications between neural cells via tunneling nanotubes

Area of Science:

• Cell Biology
• Neuroscience
• Regenerative Medicine

Background:

• Tunneling nanotubes (TNTs) are actin-based membrane structures facilitating intercellular communication, including organelle transfer.
• Peripheral nerve injury necessitates complex cell communication for effective regeneration.
• The presence and role of TNTs in the peripheral nervous system (PNS) remain largely unexplored.

Purpose of the Study:

• To investigate the existence and function of TNTs between Schwann cells (SCs) in the PNS.
• To determine the impact of TNTs on neural regeneration following injury.
• To identify molecular regulators of TNT formation in SCs.

Main Methods:

• Cultured Schwann cells (SCs) were used to study TNT formation and intercellular transfer.
• Serum depletion was employed to induce TNT-like structures in SCs.
• Rab8a and Rab11a were downregulated using genetic manipulation (siRNA/shRNA) to assess their role in TNT formation and function.
• Axonal outgrowth assays with dorsal root ganglion (DRG) neurons were performed.
• TNT-like structures were examined in sciatic nerve stumps from transected rats.

Main Results:

• Functional TNTs were observed between cultured SCs, mediating the transfer of proteins, mitochondria, and RNA.
• TNT-like structures increased in SCs under serum depletion and in injured rat sciatic nerves.
• Downregulation of Rab8a or Rab11a inhibited TNT formation, vesicle transfer, SC migration, and increased SC apoptosis.
• Knockdown of Rab8a or Rab11a in SCs suppressed axonal outgrowth from co-cultured DRG neurons.

Conclusions:

• Rab8a and Rab11a are implicated in the formation of TNTs within the PNS.
• TNTs play a significant role in peripheral nerve regeneration by regulating intercellular communication between neural and non-neural cells.
• Targeting TNTs or their regulators may offer therapeutic strategies for enhancing nerve repair.