Plastin 3 in health and disease: a matter of balance
| Autor: | Brunhilde Wirth, Ilka Müller, Daniela Mählich, Lisa Wolff, Charlotte Veltman, Eike A. Strathmann, Anja Niehoff |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Osteoclasts Review Biology Endocytosis Muscular Atrophy Spinal 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation medicine PLS3 Animals Humans Molecular Biology Cutaneous T-cell lymphomas Motor Neurons Pharmacology Membrane Glycoproteins Microfilament Proteins Cell migration Cell Biology Spinal muscular atrophy Amyotrophic lateral sclerosis medicine.disease Colorectal cancer 3. Good health Cell biology Haematopoiesis 030104 developmental biology 030220 oncology & carcinogenesis Fimbrin Osteoporosis Molecular Medicine Ataxia Signal transduction |
| Zdroj: | Cellular and Molecular Life Sciences |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-021-03843-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|