Phospholipid scramblase 1: a protein with multiple functions via multiple molecular interactors

Abstract

Phospholipid scramblase 1 (PLSCR1) is the most studied protein of the scramblase family. Originally, it was identified as a membrane protein involved in maintaining plasma membrane asymmetry. However, studies conducted over the past few years have shown the involvement of PLSCR1 in several other cellular pathways. Indeed, PLSCR1 is not only embedded in the plasma membrane but is also expressed in several intracellular compartments where it interacts with a diverse repertoire of effectors, mediators, and regulators contributing to distinct cellular processes. Although most PLSCR1 interactors are thought to be cell-type specific, PLSCR1 often exerts its regulatory functions through shared mechanisms, including the trafficking of different molecules within intracellular vesicles such as endosomes, liposomes, and phagosomes. Intriguingly, besides endogenous proteins, PLSCR1 was also reported to interact with exogenous viral proteins, thereby regulating viral uptake and spread. This review aims to summarize the current knowledge about the multiple roles of PLSCR1 in distinct cellular pathways.

Identification of a novel recurrent EEF2 gene amplification in familial prostate tumors

“…Furthermore, ZNF74 (chr22q11.21), RPL3 (chr22q13.1), ADSL (chr22q13.1), and PLSCR1 (chr3q24) all play an integral role in transcription, protein formation, and posttranscriptional modification. [29][30][31][32][33][34][35] Current literature also indicates a relationship between RPL3 and EEF2; both genes were among the top 10 hub genes identified in a differential gene expression analysis of circulating tumor cells from metastatic colorectal cancer patients. 36 Overall, our study suggests that EEF2 CNVs may lead to altered expression of genes present in key pathways that are known to be dysregulated in cancer.…”

“…It could therefore be speculated that the amplification of EEF2 results in overexpression of a nonfunctioning transcript. Furthermore, ZNF74 (chr22q11.21), RPL3 (chr22q13.1), ADSL (chr22q13.1), and PLSCR1 (chr3q24) all play an integral role in transcription, protein formation, and posttranscriptional modification 29–35 . Current literature also indicates a relationship between RPL3 and EEF2 ; both genes were among the top 10 hub genes identified in a differential gene expression analysis of circulating tumor cells from metastatic colorectal cancer patients 36 .…”

Quantitative proteomics of differentiated primary bronchial epithelial cells from chronic obstructive pulmonary disease and control identifies potential novel host factors post-influenza A virus infection

“…Next to a strong and mostly IFN signaling-related antiviral response, we discovered several influenza virus-induced proteins that have not or only recently been linked to influenza virus infection and may thus represent novel host factors in that context. PLSCR1, for instance, is an IFN-regulated gene with multiple functions including the regulation of viral uptake and replication by interacting with viral proteins at the plasma membrane as well as within the cytoplasm ( Dal Col et al, 2022 ). The few studies that addressed its role in influenza virus infection have demonstrated binding to nucleoprotein NP and prevention of its nuclear translocation ( Luo et al, 2018 ; Liu et al, 2022 ).…”

Viruses and phospholipids: Friends and foes during infection

“…It catalyzes the calcium‐induced ATP‐independent bidirectional movement of phospholipids (lipid scrambling or lipid flip‐flop) between the inner and outer leaflets of the plasma membrane, leading to the collapse of phospholipid asymmetry and phosphatidylserine externalization on the cell surface 30,31 . It is primarily found in the plasma membrane but is also transported to the nucleus and several intracellular compartments, where it interacts with various effectors, mediators, and regulators contributing to specific cellular processes 32,33 . The function of PLSCR1 in different cell compartments is described in detail in the following sections.…”

“…In addition, PLSCR1 may function as a cytoplasmic receptor for secretory leukocyte peptidase inhibitor (SLPI), which has HIV‐specific antiviral activity. Binding of SLPI by PLSCR1 modulates CD4–SLPI interaction, thus disturbing the HIV entry process 32 (Figure 1).…”