Disease relevance of VAPB

• A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis [1].
• Expanding the phenotypes of the Pro56Ser VAPB mutation: Proximal SMA with dysautonomia [2].
• Human VAP-B is involved in hepatitis C virus replication through interaction with NS5A and NS5B [3].

High impact information on VAPB

• Here, we report the finding of a novel missense mutation in the vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) gene in patients from this family [1].
• Although it was reported that the P56S mutation induces localization shift of VAPB from endoplasmic reticulum (ER) to non-ER compartments, it remains unclear what the physiological function of VAPB is and how the P56S mutation in VAPB causes motoneuronal diseases [4].
• We also show that the Nir2-VAP-B interaction attenuates protein export from the ER [5].
• In contrast, the Nir1-VAP-B interaction has no apparent effect on ER structure [5].
• VAP-A interacts with VAP-B through the transmembrane domain [3].

Biological context of VAPB

• Two frequent tetra-nucleotide repeat polymorphisms between VAPB and STX16 on chromosome 20q13 [6].
• Genetic analysis for all exons of the VAPB gene by DHPLC revealed 5 variant profiles in 83 out of 125 SALS patients [7].
• In the HCV replicon cells, the knockdown of endogenous VAP-B by small interfering RNA decreased expression of NS5B, but not of NS5A [3].
• These results suggest that VAP-B, in addition to VAP-A, plays an important role in the replication of the HCV genome [3].

Anatomical context of VAPB

• The VAPB (Pro56Ser) mutation was detected in Brazilian families with different phenotypes of motor neuron disorders [2].
• METHODS: Chondrocytes (rabbit and human fetus) and osteoblast precusors (chick embryo) were incubated in the culture medium containing VATP or VAP-A, VAP-B, and VAP-C [8].

Associations of VAPB with chemical compounds

• NS5A interacts with the coiled-coil domain of VAP-B via 70 residues in the N-terminal and 341 to 344 amino acids in the C-terminal polyproline cluster region [3].

Other interactions of VAPB

• Moreover, hVAP-A and hVAP-B associated with each other through their respective TMDs [9].
• NS5A was colocalized with VAP-B in the endoplasmic reticulum and Golgi apparatus [3].

Analytical, diagnostic and therapeutic context of VAPB

• Immunoprecipitation and mutation analyses revealed that VAP-B binds to both NS5A and NS5B in mammalian cells and forms homo- and heterodimers with VAP-A [3].

References