Data from: Neurodegenerative and neurodevelopmental roles for bulk lipid transporters VPS13A and BLTP2

Background: Bridge‐like lipid transfer proteins (BLTPs) mediate bulk lipid
transport at membrane contact sites. Mutations in BLTPs are linked to both
early‐onset neurodevelopmental and later‐onset neurodegenerative diseases,
including movement disorders. The tissue specificity and temporal
requirements of BLTPs in disease pathogenesis remain poorly understood.
Objective: The objective of this study was to determine tissue‐specific
and aging‐dependent roles for VPS13A and BLTP2 using Drosophila models.
Methods: We generated tissue‐specific knockdowns of the VPS13A ortholog
(Vps13) and the BLTP2 ortholog (hobbit) in neurons and muscles of
Drosophila. We analyzed age‐dependent locomotor behavior,
neurodegeneration, and synapse development and function. Results:
Neuron‐specific loss of the VPS13A ortholog caused neurodegeneration
followed by aging‐dependent movement deficits and reduced lifespan,
whereas muscle‐specific loss affected only lifespan. In contrast, neuronal
loss of the BLTP2 ortholog resulted in severe early‐onset locomotor
defects without neurodegeneration, whereas muscle loss impaired
synaptogenesis and neurotransmission at the neuromuscular junction.
Conclusions: VPS13A maintains neuronal survival, whereas BLTP2
orchestrates synaptic development. The phenotypic specificity of BLTP
function provides mechanistic insights into distinct disease trajectories
for BLTP‐associated disorders.