Differential regulation of endoplasmic reticulum structure through VAP-Nir protein interaction.
The endoplasmic reticulum (ER) exhibits a characteristic tubular structure that is dynamically rearranged in response to specific physiological demands. However, the mechanisms by which the ER maintains its characteristic structure are largely unknown. Here we show that the integral ER-membrane protein VAP-B causes a striking rearrangement of the ER through interaction with the Nir2 and Nir3 proteins. We provide evidence that Nir (Nir1, Nir2, and Nir3)-VAP-B interactions are mediated through the conserved FFAT (two phenylalanines (FF) in acidic tract) motif present in Nir proteins. However, each interaction affects the structural integrity of the ER differently. Whereas the Nir2-VAP-B interaction induces the formation of stacked ER membrane arrays, the Nir3-VAP-B interaction leads to a gross remodeling of the ER and the bundling of thick microtubules along the altered ER membranes. In contrast, the Nir1-VAP-B interaction has no apparent effect on ER structure. We also show that the Nir2-VAP-B interaction attenuates protein export from the ER. These results demonstrate new mechanisms for the regulation of ER structure, all of which are mediated through interaction with an identical integral ER-membrane protein.
Amarilio
Roy
R
Neurobiology Department, Weizmann Institute of Science, Rehovot 76100, Israel.
Ramachandran
Sreekumar
S
Sabanay
Helena
H
Lev
Sima
S
D020816:Amino Acid Motifs; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051605:Kv Channel-Interacting Proteins; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D033921:Vesicular Transport Proteins
D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D051605:Kv Channel-Interacting Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C113505:PITPNM1 protein, human; C117888:PITPNM2 protein, human; C496748:VAPB protein, human; D033921:Vesicular Transport Proteins