Courier service for phosphatidylinositol: PITPs deliver on demand

Abstract

Phosphatidylinositol is the parent lipid for the synthesis of seven phosphorylated inositol lipids and each of them play specific roles in numerous processes including receptor-mediated signalling, actin cytoskeleton dynamics and membrane trafficking. PI synthesis is localised to the endoplasmic reticulum (ER) whilst its phosphorylated derivatives are found in other organelles where the lipid kinases also reside. Phosphorylation of PI to phosphatidylinositol (4,5) bisphosphate (PI(4,5)P 2 ) at the plasma membrane and to phosphatidylinositol 4-phosphate (PI4P) at the Golgi are key events in lipid signalling and Golgi function respectively. Here we review a family of proteins, phosphatidylinositol transfer proteins (PITPs), that can mobilise PI from the ER to provide the substrate to the resident kinases for phosphorylation. Recent studies identify specific and overlapping functions for the three soluble PITPs (PITPα, PITPβ and PITPNC1) in phospholipase C signalling, neuronal function, membrane trafficking, viral replication and in cancer metastases.

Aberrant overexpression of HOTAIR inhibits abdominal adipogenesis through remodelling of genome-wide DNA methylation and transcription

“…Among these 10 genes, 5 genes were selected for evaluation because their functions are associated with adipocyte differentiation, neuronal development or cellular assembly: PITPNC1 is involved in lipid metabolism [ 27 ]; SLITRK4 modulates synapse differentiation [ 28 ]; ENOX1 regulates plasma membrane electron transport pathways [ 29 ]; GRTP1 encodes a GTPase activator protein [ 30 ]; and gelsolin ( GSN ) is a key regulator of actin filament assembly [ 31 ]. We first measured their expression ( PITPNC1, SLITRK4, ENOX1, GRTP1 and GSN ) using real-time qPCR in Abd HOTAIR-OE and Control cells on day 0, 4, 7 and 14 of adipogenesis.…”

“…The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) gene, located on chromosome 17, encodes the PITPNC1 protein belonging to the phosphatidylinositol transfer protein (PITP) family. PITPs can mobilize phosphatidylinositol (PI) from the endoplasmic reticulum to the resident kinase for phosphorylation and are involved in multiple cellular processes, including cell signalling, membrane trafficking, cytoskeletal remodelling, and lipid metabolism [ 27 ]. PITPNC1 was ubiquitously expressed in multiple tissues, with adipose tissue ranked as the top tissue, followed by the basal ganglia, breast, lung, and cerebral cortex based on Human Protein Atlas GTEx (Genotype-Tissue Expression) data (RNA-seq data on RSEMv1.2.22 (v7)).…”

“…PITPNC1 was ubiquitously expressed in multiple tissues, with adipose tissue ranked as the top tissue, followed by the basal ganglia, breast, lung, and cerebral cortex based on Human Protein Atlas GTEx (Genotype-Tissue Expression) data (RNA-seq data on RSEMv1.2.22 (v7)). In addition, the PITPNC1 protein is a soluble PITP and unique for its high binding affinity with phosphatidic acid (PA), but its functional significance has just started to be studied [ 27 , 52 ]. Recently, PITPNC1 was found to be highly expressed in omental metastatic lesions of gastric cancer and upregulated by omental adipocytes [ 53 ], indicating that it might influence the association between obesity and cancers.…”

Organelle-selective click labeling coupled with flow cytometry allows high-throughput CRISPR screening of genes involved in phosphatidylcholine metabolism

“…A potential limitation of O-ClickFC is that the steric hindrance of the methylazide group of N 3 -PC might prevent biological processes mediated by critical interactions between the choline head group of PC and proteins. However, we successfully captured PITPNB and STARD7 (Figure 5C,J), both of which recognize the choline head group of PC and selectively transport it between organelle membranes (Ashlin et al, 2021; Haberkant et al, 2013; Horibata and Sugimoto, 2010; Vordtriede et al, 2005). Detection of these two hits indicates that the biological impact of azido group incorporation is minimal or negligible.…”

Role of the Mosaic Cisternal Maturation Machinery in Glycan Synthesis and Oncogenesis

“…PI synthesis occurs in the ER, and PI transfer proteins such as PITPNC1 play an important role in delivering PI to the Golgi apparatus acting at the ER-Golgi interface ( Ashlin et al, 2021 ). PITPNC1 is known to contribute to several oncogenic effects such as tumor angiogenesis, metastasis, and malignant secretion in breast cancer, omental metastasis of gastric cancer and in the development of radio-resistance in colorectal cancer ( Tan et al, 2018 ; Tan Y. et al, 2020 ).…”