Plasmolipin and Its Role in Cell Processes

Abstract

The mechanisms involved in the origin and development of malignant and neurodegenerative diseases are an important area of modern biomedicine. A crucial task is to identify new molecular markers that are associated with rearrangements of intracellular signaling and can be used for prognosis and the development of effective treatment approaches. The proteolipid plasmolipin (PLLP) is a possible marker. PLLP is a main component of the myelin sheath and plays an important role in the development and normal function of the nervous system. PLLP is involved in intracellular transport, lipid raft formation, and Notch signaling. PLLP is presumably involved in various disorders, such as cancer, schizophrenia, Alzheimer’s disease, and type 2 diabetes mellitus. PLLP and its homologs were identified as possible virus entry receptors. The review summarizes the data on the PLLP structure, normal functions, and role in diseases.

Transition of allele-specific DNA hydroxymethylation at regulatory loci is associated with phenotypic variation in monozygotic twins discordant for psychiatric disorders

“…6 B) in SK-SN-SH cells. PLLP encodes the proteolipid plasmolipin, which is a main component of synaptic plasma membranes and myelin sheaths and is involved in intracellular transport and neurite growth [ 49 ]. We then observed that rs4558409-KO promoted all-trans retinoic acid (ATRA)-induced neural development (Fig.…”

“…Our study validated the biological role of AShM transitions at the PLLP rs4558409 locus, leading to alterations in POU3F2 binding ability and contributing to the downregulation of PLLP , providing etiological implications for SCZ or BPD. PLLP encodes the proteolipid plasmolipin, which is a main component of synaptic plasma membranes and myelin sheaths and is involved in intracellular transport and neurite growth [ 49 ]. AShM transitions at the PLLP rs4558409 locus across PDC twin pairs reduced PLLP transcriptional activity through hydroxymethylation-mediated inhibition of active POU3F2 binding affinity at the active T allele of the rs4558409 (G/T) regulatory locus.…”

“…In fact, rs4558409 is a subthreshold GWAS SNP associated with SCZ ( p =0.007479 in PGC3) [ 36 ] and MDD ( p =0.026) [ 40 ], and hyper-hydroxymethylation at the risk alternative T allele of rs4558409 (G/T), which reduced TF binding affinity and PLLP expression, might increase disease susceptibility. PLLP plays an important role in membrane biogenesis and myelination [ 49 ], and distorted oligodendrocyte differentiation and subsequent defects in myelination might lead to SCZ and BPD onset [ 49 , 53 ]. Intriguingly, POU3F2 is one of the key regulators coexpressed with many genes within the SCZ-related module [ 54 ], and POU3F2 -regulated target genes may contribute to neurodevelopment and synaptic function in various ways [ 55 ].…”

The MAL Family of Proteins: Normal Function, Expression in Cancer, and Potential Use as Cancer Biomarkers

“…PLLP was initially isolated from plasma membranes of bovine kidney plasma membrane [39] and was later characterized as a component of synaptic plasma membranes, myelin sheaths, and endocytic vesicles [4,40]. PLLP, which mostly distributes in subapical endosomes, is required for apical endocytosis and endosomal maturation [41,42], and acts in the recycling of apical proteins from sorting endosomes to the apical membrane (Figure 2D).…”

“…A computational analysis of transcriptomic data showed MAL2 to be one of the strongest hub genes involved in signaling pathways in diabetes type 2 connected to tuberculosis and rheumatoid arthritis, although the contribution (if any) of MAL2 to the disease is unknown [57]. Altered PLLP expression has been related to a number of neurological diseases (e.g., schizophrenia, depressive disorder, and Alzheimer's disease), diabetes type 2, cornea degeneration, lung sarcoidosis, and hyperalphalipoproteinemia [40]. A number of transcriptome-wide meta-analyses aimed at identifying genes involved in hypertension detected MYADM as a candidate [58][59][60].…”