COL4A3BP (F5U2Y) Rabbit mAb #56098

Non-vesicular transport of ceramide from the endoplasmic reticulum (ER) to the Golgi requires the activity of collagen type IV alpha-3-binding protein (COL4A3BP), also known as ceramide transfer protein (CERT1) or StAR-related lipid transfer protein 11 (StARD11) (1). COL4A3BP contains an N-terminal pleckstrin homology (PH) domain that targets the protein to the Golgi, a central FFAT domain that directly binds to ER proteins VAPA and VAPB, and a C-terminal START domain that extracts ceramide from ER membranes (1-3). Phosphorylation of COL4A3BP at Ser132 by protein kinase D reduces COL4A3BP activity by inducing an autoinhibitory interaction between the PH and START domains (4,5). Sterol-sensitive activation of COL4A3BP requires desphosphorylation at Ser132 and direct interactions with both oxysterol-binding protein (OSBP) and VAPA (5,6). Silencing of COL4A3BP sensitizes cells to ER stress (7) and causes ceramide mislocalization to mitochondria, disrupting mitochondrial membranes (3). COL4A3BP mutations, including Ser132Leu or Gly243Arg, enhance the protein's activity, causing constitutive Golgi localization and disruption of sphingolipid homeostasis (8,9). These mutations are associated with inherited intellectual disability (ID) in humans (8,9).