Disease relevance of PLS3

• Therefore, T-plastin has the potential to be a Sezary cell-specific marker valuable for diagnostic and treatment of Sezary syndrome [1].
• It was discovered that unlike T-helper cells from healthy individuals or patients with nonmalignant dermatoses, Sezary cells from most patients with Sezary syndrome aberrantly expressed T-plastin mRNA and protein [1].
• T-plastin is an actin-bundling protein and is known to be highly expressed in actively dividing cells and up-regulated in several carcinomas [2].
• Cytoskeletal rearrangements and the functional role of T-plastin during entry of Shigella flexneri into HeLa cells [3].
• We report here that SipA forms a complex with T-plastin on bacterial infection [4].
• PLS3 is a protective modifier of spinal muscular atrophy (SMA). Only females but not males with homozygous deletions of SMN1 and 3-4 copies of SMN2 are protected against SMA when PLS3 is highly expressed [5].

Psychiatry related information on PLS3

• The findings suggest that the PLS-3 is generally an informative language test for African American preschoolers; however, scores should be interpreted with caution [6].
• At 21 months, child cognitive and language development and parent-child interaction were assessed by the Bayley Mental Development Index (MDI), the Preschool Language Scale-3 (PLS-3), and the Caregiver-Child Interaction Rating Scale, respectively [7].

High impact information on PLS3

• By transient expression of a truncated T-plastin which is deprived of one of its actin-binding sites, we also demonstrate the functional role of T-plastin in Shigella entry into HeLa cells [3].
• L-plastin remains associated with microfilaments while T-plastin is almost completely extracted after treatment of the cells with non-ionic detergent [8].
• We also report that T-plastin is recruited to S. typhimurium-induced membrane ruffles by a CDC42-dependent signaling process and is required for bacterial entry [4].
• The I-plastin gene was mapped by PCR to human chromosome 3; the L- and T-plastin genes were previously mapped to chromosomes 13 and X, respectively [9].
• In contrast to the situation for the intestine, high levels of L- and T-plastin mRNAs were detected in Caco-2, a human colon-derived cell line [9].

Biological context of PLS3

• L- and T-plastin genes were also mapped to chromosomes 13 and X, respectively, using polymerase chain reaction amplification with isoform-specific probes [10].
• Here, we analyse the effects of T-plastin/T-fimbrin, a representative member of an important actin-filament cross-linking protein by combining a quantitative biomimetic motility assay with biochemical and cell-based approaches [11].
• The down-regulation of T-plastin expression is further demonstrated in human trophoblastic BeWo cells induced to differentiate using transforming growth factor (TGF)beta1, a growth factor known for its anti-proliferative and anti-invasive response in placental cells [2].
• Using this approach, T-plastin was initially identified as being differentially expressed in the human first-trimester placenta [2].
• Expression of PLS3(T21A) in cells could not enhance AD198-induced apoptosis compared with expression of the wild-type PLS3 [12].
• PLS3 is highly expressed in spinal cord and motor neurons, particularly in the filopodia of the growth cones [5].

Anatomical context of PLS3

• In contrast, L-plastin expression was restricted to the spleen and other lymph node-containing organs, while T-plastin was expressed in a variety of organs, including muscle, brain, uterus, and esophagus [9].
• Expression of the L-plastin isoform appears to be restricted to replicating blood cells, and the two T-plastin isoforms appear to be restricted to replicating cells of solid tissues [13].
• In addition, 4 tumor cell lines that were L-plastin-negative exhibited evidence of defective T-plastin expression increasing the apparent co-incidence of plastin abnormalities associated with human tumorigenesis to 71% [10].
• Changes in T-plastin expression with human trophoblast differentiation [2].
• During apoptosis, activated protein kinase C-delta (PKC-delta) translocates to mitochondria and phosphorylates PLS3 [12].

Associations of PLS3 with chemical compounds

• The phosphorylated threonine was mapped to Thr21 of PLS3 [12].
• Here, we utilize an extranuclear-targeted anthracycline N-benzyladriamycin-14-valerate (AD198), a PKC-delta activator, to investigate the mechanism of PLS3 phosphorylation by PKC-delta [12].
• Using benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone and cyclosporine A, we also showed that AD198-induced PLS3 phosphorylation occurs upstream of caspase activation and independent of mitochondrial permeability transition [12].
• Mutation of Thr21 to alanine did not affect mitochondrial localization of PLS3 but abolished threonine phosphorylation by PKC-delta in vitro and AD198-induced PLS3 phosphorylation in vivo [12].
• PLS3 (phospholipid scramblase-3) is a new member of the family of phospholipid scramblases and transports CL (cardiolipin) from the inner to the outer mitochondrial membrane [14].

Regulatory relationships of PLS3

• T-Plastin also decreased the F-actin disassembly rate and inhibited cofilin-mediated depolymerization of actin filaments in vitro [11].
• PLS3 increases the ratio of F/G-actin [5].

Other interactions of PLS3

• Actin-filament cross-linking protein T-plastin increases Arp2/3-mediated actin-based movement [11].
• T-Plastin increased the velocity of VCA beads 1.5 times, stabilized actin comets and concomitantly displaced cofilin, an actin-depolymerizing protein [11].
• Phospholipid scramblase 3 (PLS3) is an enzyme that plays a critical role in mitochondrial morphology, functions, and apoptotic response [12].
• We identified a Rev-like nuclear export sequence (NES) in T-plastin that is able to export an otherwise nuclear protein in an LMB-dependent manner [15].
• Differential regulation of human T-plastin gene in leukocytes and non-leukocytes: identification of the promoter, enhancer, and CpG island [16].

Analytical, diagnostic and therapeutic context of PLS3

• DNA footprinting identified the T-plastin enhancer as two inverted symmetric octamers (AGATAACCTC and GAGGTCAGCT) separated by 17 nucleotides [16].
• Increased expression of T-plastin gene in cisplatin-resistant human cancer cells: identification by mRNA differential display [17].

References