Membrane remodeling by FAM92A1 during brain development regulates neuronal morphology, synaptic function, and...

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• The physiological role of Bin/Amphiphysin/Rvs (BAR) domain protein FAM92A1 in the brain is largely unknown.
• FAM92A1 is known to regulate mitochondrial ultrastructure and ciliogenesis.

Purpose of the Study:

• To elucidate the function of FAM92A1 in the mammalian brain.
• To investigate the molecular mechanisms underlying FAM92A1's role in neural function.

Main Methods:

• FAM92A1 knockout mouse model generation and analysis.
• Assessment of brain morphology, cognitive function, and synaptic plasticity.
• Crystal structure determination of the FAM92A1 BAR domain.
• Atomistic molecular dynamics simulations of FAM92A1-membrane interactions.

Main Results:

• FAM92A1 is expressed in developing neurons.
• FAM92A1 knockout mice exhibit altered brain morphology, age-associated cognitive deficits, neuronal degeneration, and impaired synaptic plasticity.
• FAM92A1 deficiency disrupts neuronal membrane structures, including mitochondrial inner membranes, myelin sheaths, and synapses.
• FAM92A1 binds to phosphoinositide- and cardiolipin-containing membranes, inducing lipid clustering and membrane curvature.

Conclusions:

• FAM92A1 plays a vital physiological role in the brain.
• FAM92A1 regulates neuronal membrane remodeling and endocytic processes, impacting synaptic plasticity and overall neural function.