The VAPs (VAMP-associated proteins) are highly conserved integral endoplasmic reticulum (ER)-membrane proteins, implicated in diverse cellular functions, including regulation of lipid transport and homeostasis, membrane trafficking, neurotransmitter release, stabilization of presynaptic microtubules, and the unfolded protein response (UPR).
A single missense mutation within the human VAP-B gene was identified in three forms of the familial motor-neuron disease (MND) including amyotrophic lateral sclerosis (ALS). The mutation substitutes a highly conserved proline residue at position 56 with a serine (P56S) and causes motor-neuron degeneration by an as-yet-unknown mechanism. Prof. Sima Lev and her team discovered that the P56S mutation induces conformational changes in VAP-B, which facilitates its aggregation and consequently inhibits its physiological function.
Read the presentation of Prof. Sima Lev: