Munc18 and Munc13 regulate early neurite outgrowth

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• Neuronal growth cones utilize vesicular secretion proteins like SNAREs, Munc13, and Munc18.
• Vesicle fusion in growth cones may facilitate neuronal outgrowth before synapse formation.

Purpose of the Study:

• To investigate the role of vesicle fusion proteins (Munc18-1, Munc13-1/2) in neuronal outgrowth.
• To determine if impaired vesicle fusion affects neurite outgrowth speed and growth cone morphology.

Main Methods:

• Utilized dissociated cell and organotypic slice cultures from Munc18-1 null and Munc13-1/2 double null mice.
• Assessed neurite length and growth cone filopodia during early development (DIV1-4) and after synaptogenesis (DIV14-23).

Main Results:

• Release-deficient neurons exhibited decreased outgrowth speed and reduced total neurite length in early development.
• Munc18-1 null neurons showed increased filopodia, unlike wild-type or Munc13-1/2 double null neurons.
• The reduction in neurite length was not observed after synaptogenesis.

Conclusions:

• Vesicle fusion is critical for initial neuronal outgrowth but not essential during or after synaptogenesis.
• Outgrowth speed may not be rate-limiting for neuronal network formation in vitro.
• Munc18, but not Munc13, regulates growth cone filopodia, potentially through actin dynamics.