Plastin Family of Actin-Bundling Proteins: Its Functions in Leukocytes, Neurons, Intestines, and Cancer

Shinomiya, Hiroto

doi:10.1155/2012/213492

Cited by 110 publications

(122 citation statements)

References 70 publications

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“…(39) Plastin 3 is ubiquitously expressed in solid tissues and the actin cytoskeleton is a key feature of all cells. (10) PLS3 knockdown in zebrafish leads to a lethal phenotype. (42) It is therefore surprising that the phenotype in humans with PLS3 mutations is relatively mild and apparently limited to the skeleton.…”

Section: Discussionmentioning

confidence: 99%

Osteoporosis Caused by Mutations in PLS3: Clinical and Bone Tissue Characteristics

Fahiminiya

Majewski

Al-Jallad

et al. 2014

Journal of Bone and Mineral Research

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Mutations in PLS3 have been identified as a cause of bone fragility in children, but the bone phenotype associated with PLS3 mutations has not been reported in detail. PLS3 is located on the X chromosome and encodes the actin-binding protein plastin 3. Here we describe skeletal findings in 4 boys from 2 families with mutations in PLS3 (c.994_995delGA; p.Asp332 Ã in family 1; c.1433T > C; p. Leu478Pro in family 2). When first evaluated between 4 and 8 years of age, these boys had a history of one to four long-bone fractures. Mild vertebral compression fractures were identified in each boy. No obvious extraskeletal disease manifestations were present. Lumbar spine areal bone mineral density (LS-aBMD) Z-scores ranged from -1.7 to -3.5, but height was normal. Iliac bone histomorphometry in 2 patients showed low trabecular bone volume and a low osteoid maturation time but normal bone formation rate and osteoclast surface. Quantitative backscattered electron imaging (qBEI) did not reveal a major abnormality in bone mineralization density distribution. The 2 boys from family 1 received oral alendronate for 6 years, which normalized LS-aBMD. The mothers of the 4 boys did not have a history of fractures and had normal LS-aBMD. However, one of these mothers had low bone mass at the distal radius, as measured by peripheral quantitative computed tomography (pQCT). In conclusion, hemizygous mutations in PLS3 are associated with osteoporosis and bone fragility in childhood, but in contrast to bone fragility caused by mutations in collagen type I encoding genes, there is no hypermineralization of mineralized bone matrix.

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Section: Discussionmentioning

confidence: 99%

Osteoporosis Caused by Mutations in PLS3: Clinical and Bone Tissue Characteristics

Fahiminiya

Majewski

Al-Jallad

et al. 2014

Journal of Bone and Mineral Research

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“…LCP1 is over-expressed in many different cancers and may be involved in cell mobility (Shinomiya 2012;Van Audenhove et al 2016). Although little is known about the molecular mechanisms that regulate LCP1 transcription and translation, a variant in the promoter region of LCP1 causes a decreased risk for prostrate cancer (Chen et al 2016) while other variants in LCP1 are proposed as biomarkers for colorectal cancer recurrence and eQTLs (Garge et al 2010;Ning et al 2014).…”

Section: Structured Coding Region Of Lcp1 Mrnamentioning

confidence: 99%

“…Approximately 15% of inherited SNVs change RNA structure in family trio transcriptome-wide structural experiments (Wan et al 2014). However, in general the function of structure in messenger RNAs (mRNAs) is unclear (Bartel 2009;Scharff et al 2011;Dethoff et al 2012;Li et al Lackey 4 structured as TPT1, LCP1 (Lymphocyte cytosolic protein 1) is also over-expressed in many different cancers and may be involved in cell mobility (Shinomiya 2012;Van Audenhove et al 2016). …”

Section: Introductionmentioning

confidence: 99%

Allele-specific SHAPE-MaP assessment of the effects of somatic variation and protein binding on mRNA structure

Lackey

Coria

Woods

et al. 2018

RNA

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The precise impact of inherited and somatic mutations on messenger RNA (mRNA) structure remains poorly understood. Recent technological advances that leverage next generation sequencing to obtain experimental structure data, such as SHAPE-MaP (Selective 2' Hydroxyl Acylation by Primer Extension and Mutational Profiling), can reveal structural effects of mutations especially when this data is rigorously incorporated in RNA structural modeling. Here we analyze the ability of SHAPE-MaP to detect the relatively subtle structural changes caused by single nucleotide mutations. We find that allele-specific sorting greatly improved the detection ability of SHAPE-MaP. Thus, we used SHAPE-MaP with a novel combination of clone-free robotic mutagenesis and allele-specific sorting to perform a rapid, comprehensive survey of non-coding somatic and inherited riboSNitches in two cancer-associated mRNAs, TPT1 and LCP1. Combined with rigorous thermodynamic modeling of the Boltzmann suboptimal ensemble we identified a subset of somatic and Lackey 2 inherited mutations that change TPT1 and LCP1 RNA structure, with approximately 14% of all variants identified acting as riboSNitches. To confirm that these in vitro structures were biologically relevant, we tested how dependent TPT1 and LCP1 mRNA structures are on their environments. We performed SHAPE-MaP on TPT1 and LCP1 mRNAs in the presence or absence of cellular proteins and found that both TPT1 and LCP1 have similar overall folds in all conditions. RiboSNitches identified within these mRNAs in vitro are likely to exist under biological conditions. Overall, these data reveal a remarkably robust mRNA structural landscape where differences in environmental conditions and most sequence variants do not significantly alter RNA structural ensembles. Finally, predicting riboSNitches in mRNAs from sequence alone remains particularly challenging; these data will provide the community with a benchmark for further algorithmic development.

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“…Phosphorylation on Ser-5 on the other hand increases F-actin binding (23). Although the ubiquitous T-plastin isoform is expressed in solid tissue-derived cells, L-plastin is restricted to hematopoietic cells (24). However, the L-plastin gene is activated in most human cancer cell lines (25) and ectopic expression was observed in over half of the epithelial and mesenchymal tumors examined (26).…”

mentioning

confidence: 99%

Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia

Audenhove¹,

Denert²,

Boucherie³

et al. 2016

Journal of Biological Chemistry

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Invadopodia and filopodia are dynamic, actin-based protrusions contributing to cancer cell migration, invasion, and metastasis. The force of actin bundles is essential for their protrusive activity. The bundling protein fascin is known to play a role in both invadopodia and filopodia. As it is more and more acknowledged that functionally related proteins cooperate, it is unlikely that only fascin bundles actin in these protrusions. Another interesting candidate is L-plastin, normally expressed in hematopoietic cells, but considered a common marker of many cancer types. We identified L-plastin as a new component of invadopodia, where it contributes to degradation and invasiveness. By means of specific, high-affinity nanobodies inhibiting bundling of fascin or L-plastin, we further unraveled their cooperative mode of action. We show that the bundlers cannot compensate for each other due to strikingly different bundling characteristics: L-plastin bundles are much thinner and less tightly packed. Composite bundles adopt an intermediate phenotype, with fascin delivering the rigidity and strength for protrusive force and structural stability, whereas L-plastin accounts for the flexibility needed for elongation. Consistent with this, elevated L-plastin expression promotes elongation and reduces protrusion density in cells with relatively lower L-plastin than fascin levels.Filopodia are finger-like protrusions coordinating movement at the cell front by "sensing" extracellular stimuli (1). Invadopodia on the other hand are formed at the ventral cell side, enabling matrix degradation by localized proteolysis (2). As both actin-based protrusions contribute to migration and invasion, they are associated with cancer metastasis (3, 4), which has also been shown in vivo (5, 6).The architecture and dynamics of filopodia and invadopodia are controlled by a broad variety of actin-binding proteins (7,8). Moreover, these regulating proteins show highly similar spatial and temporal distributions in filopodia and invadopodia (9).

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Plastin Family of Actin-Bundling Proteins: Its Functions in Leukocytes, Neurons, Intestines, and Cancer

Cited by 110 publications

References 70 publications

Osteoporosis Caused by Mutations in PLS3: Clinical and Bone Tissue Characteristics

Osteoporosis Caused by Mutations in PLS3: Clinical and Bone Tissue Characteristics

Allele-specific SHAPE-MaP assessment of the effects of somatic variation and protein binding on mRNA structure

Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia

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