Phosphatidylinositol transfer proteins (PITPs) are essential regulators of PLC signalling. The PI transfer domain (PITPd) of multi-domain PITPs is reported to be sufficient for function, questioning the relevance of other domains in the protein. In photoreceptors, loss of RDGBα, a multi-domain PITP localized to membrane contact sites (MCSs), results in multiple defects during PLC signalling. Here, we report that the PITPd of RDGBα does not localize to MCSs and fails to support function during strong PLC stimulation. We show that the MCS localization of RDGBα depends on the interaction of its FFAT motif with dVAP-A. Disruption of the FFAT motif (RDGB) or downregulation of dVAP-A, both result in mis-localization of RDGBα and are associated with loss of function. Importantly, the ability of the PITPd in full-length RDGB to rescue mutant phenotypes was significantly worse than that of the PITPd alone, indicating that an intact FFAT motif is necessary for PITPd activity Thus, the interaction between the FFAT motif and dVAP-A confers not only localization but also intramolecular regulation on lipid transfer by the PITPd of RDGBα. This article has an associated First Person interview with the first author of the paper.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818063 | PMC |
| http://dx.doi.org/10.1242/jcs.207985 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
XopM, An FFAT Motif-Containing Type III Effector Protein From Xanthomonas, Suppresses MTI Responses at the Plant Plasma Membrane.
Mol Plant Pathol
December 2024
Plant Metabolism Group, Leibniz-Institute of Vegetable and Ornamental Crops (IGZ), Großbeeren, Germany.
Article Synopsis
- Many gram-negative pathogenic bacteria, like Xanthomonas campestris pv. vesicatoria (Xcv), utilize type III effector proteins (T3Es) to manipulate host immunity, with XopM being a core T3E whose specific function was previously unknown.
- XopM interacts specifically with vesicle-associated membrane proteins (VAPs) via two FFAT motifs, which are critical for its ability to target plant membranes and potentially disrupt immune responses.
- When introduced into plants, XopM not only supports nonpathogenic bacterial growth but also reduces reactive oxygen species production, indicating its role in suppressing plant immunity during infection.
Making contact away from home: a bacterial secreted effector mediates inter-organelle communication.
EMBO Rep
December 2024
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
Inter-organelle communication via the formation of membrane contact sites (MCS) is essential for cell homeostasis. Bacterial pathogens residing in membrane bound vacuoles have exploited this biological process by secreting effector proteins that establish and function at MCS between their vacuole and host organelles. In this issue of EMBO reports, Angara et al (2024) identify a effector protein, CbEPF1, that uses molecular mimicry of eukaryotic FFAT motifs to alter MCS between two host organelles: the endoplasmic reticulum and lipid droplets.
View Article and Find Full Text PDFA novel bacterial effector protein mediates ER-LD membrane contacts to regulate host lipid droplets.
EMBO Rep
December 2024
Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Effective intracellular communication between cellular organelles occurs at dedicated membrane contact sites (MCSs). Tether proteins are responsible for the establishment of MCSs, enabling direct communication between organelles to ensure organelle function and host cell homeostasis. While recent research has identified tether proteins in several bacterial pathogens, their functions have predominantly been associated with mediating inter-organelle communication between the bacteria containing vacuole (BCV) and the host endoplasmic reticulum (ER).
View Article and Find Full Text PDFNew insights into the functions of ACBD4/5-like proteins using a combined phylogenetic and experimental approach across model organisms.
Biochim Biophys Acta Mol Cell Res
December 2024
Biosciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK. Electronic address:
Acyl-CoA binding domain-containing proteins (ACBDs) perform diverse but often uncharacterised functions linked to cellular lipid metabolism. Human ACBD4 and ACBD5 are closely related peroxisomal membrane proteins, involved in tethering of peroxisomes to the ER and capturing fatty acids for peroxisomal β-oxidation. ACBD5 deficiency causes neurological abnormalities including ataxia and white matter disease.
View Article and Find Full Text PDFThe Ribosome Assembly Factor LSG1 Interacts with Vesicle-Associated Membrane Protein-Associated Proteins (VAPs).
Mol Cell Biol
September 2024
Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, USA.
LSG1 is a conserved GTPase involved in ribosome assembly. It is required for the eviction of the nuclear export adapter NMD3 from the pre-60S subunit in the cytoplasm. In human cells, LSG1 has also been shown to interact with vesicle-associated membrane protein-associated proteins (VAPs) that are found primarily on the endoplasmic reticulum.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!