The PTPIP51 coiled-coil domain is important in VAPB binding, formation of ER-mitochondria contacts and IP3 receptor delivery of Ca2+ to mitochondria

• DOI: 10.3389/fcell.2022.920947
• Publication Date: 2022-08-31T08:34:32Z
• Authors: Gábor M. Mórotz; Sandra M. Martín-...; Andrea Markovinovic; Sebastien Paillusson; Matthew R. G. Rus...; Pedro M. Pereira ...; Roland A. Fleck; Wendy Noble; Christopher C.J. ...
• Keywords: Coiled coil

Signaling between the endoplasmic reticulum (ER) and mitochondria regulates a number of fundamental physiological processes. This signaling involves close physical contacts two organelles that are mediated by VAPB-PTPIP51 ″tethering” proteins. The tethers facilitate inositol 1,4,5-trisphosphate (IP3) receptor delivery Ca 2+ from ER to mitochondria. Damage is seen in Alzheimer’s disease, Parkinson’s disease frontotemporal dementia with related amyotrophic lateral sclerosis (FTD/ALS). Understanding mechanisms regulate VAPB‐PTPIP51 interaction thus represents an important area research. Recent studies suggest FFAT motif PTPIP51 key its binding VAPB but this work relies on vitro short peptides. Cellular support notion full-length proteins lacking. Here we address issue. Immunoprecipitation assays transfected cells revealed deletion has little effect binding. However, mutation nearby coiled-coil domain markedly affect Using electron microscopy, then show not abrogates ER-mitochondria contacts. Finally, IP3 receptor-mediated Thus, essential for functions.