Plastin 3 in health and disease: a matter of balance.
Lisa WolffEike A StrathmannIlka MüllerDaniela MählichCharlotte VeltmanAnja NiehoffBrunhilde WirthPublished in: Cellular and molecular life sciences : CMLS (2021)
For a long time, PLS3 (plastin 3, also known as T-plastin or fimbrin) has been considered a rather inconspicuous protein, involved in F-actin-binding and -bundling. However, in recent years, a plethora of discoveries have turned PLS3 into a highly interesting protein involved in many cellular processes, signaling pathways, and diseases. PLS3 is localized on the X-chromosome, but shows sex-specific, inter-individual and tissue-specific expression variability pointing towards skewed X-inactivation. PLS3 is expressed in all solid tissues but usually not in hematopoietic cells. When escaping X-inactivation, PLS3 triggers a plethora of different types of cancers. Elevated PLS3 levels are considered a prognostic biomarker for cancer and refractory response to therapies. When it is knocked out or mutated in humans and mice, it causes osteoporosis with bone fractures; it is the only protein involved in actin dynamics responsible for osteoporosis. Instead, when PLS3 is upregulated, it acts as a highly protective SMN-independent modifier in spinal muscular atrophy (SMA). Here, it seems to counteract reduced F-actin levels by restoring impaired endocytosis and disturbed calcium homeostasis caused by reduced SMN levels. In contrast, an upregulation of PLS3 on wild-type level might cause osteoarthritis. This emphasizes that the amount of PLS3 in our cells must be precisely balanced; both too much and too little can be detrimental. Actin-dynamics, regulated by PLS3 among others, are crucial in a lot of cellular processes including endocytosis, cell migration, axonal growth, neurotransmission, translation, and others. Also, PLS3 levels influence the infection with different bacteria, mycosis, and other pathogens.
Keyphrases
- cell proliferation
- cell migration
- induced apoptosis
- wild type
- postmenopausal women
- healthcare
- bone mineral density
- gene expression
- signaling pathway
- binding protein
- magnetic resonance
- public health
- bone marrow
- oxidative stress
- magnetic resonance imaging
- risk assessment
- dna methylation
- protein protein
- squamous cell carcinoma
- climate change
- adipose tissue
- epithelial mesenchymal transition
- multidrug resistant
- social media
- copy number
- small molecule
- genome wide
- cell death
- insulin resistance
- health information
- optical coherence tomography
- high fat diet induced