Mechanosensitive ion channels: molecules of mechanotransduction

Martinac, Boris

doi:10.1242/jcs.01232

Cited by 487 publications

(365 citation statements)

References 143 publications

(192 reference statements)

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“…The other two are microsporidian-specific orthologs (OG5_182073 and OG5_188308): a protein containing a mechanosensitive (MS) ion channel domain (PF00924) and another containing a Sec6 exocyst component domain (PF06046). MS ion channels have a variety of roles in the physiology of eukaryotic cells, such as osmotic gradients, cell swelling, gravitropism, and control of cellular turgor (34). We speculate that the microsporidian-specific MS channel could be used for spore germination, which involves increased intrasporal osmotic pressure (29).…”

Section: Resultsmentioning

confidence: 99%

Evolution of a morphological novelty occurred before genome compaction in a lineage of extreme parasites

Haag

James

Pombert

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

118

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Significance Intracellular obligate parasitism results in extreme adaptations, whose evolutionary history is difficult to understand, because intermediate forms are hardly ever found. Microsporidia are highly derived intracellular parasites that are related to fungi. We describe the evolutionary history of a new microsporidian parasite found in the hindgut epithelium of the crustacean Daphnia and conclude that the new species has retained ancestral features that were lost in other microsporidia, whose hallmarks are the evolution of a unique infection apparatus, extreme genome reduction, and loss of mitochondrial respiration. The first evolutionary steps leading to the extreme metabolic and genomic simplification of microsporidia involved the adoption of a parasitic lifestyle, the development of a specialized infection apparatus, and the loss of diverse regulatory proteins.

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Section: Resultsmentioning

confidence: 99%

Evolution of a morphological novelty occurred before genome compaction in a lineage of extreme parasites

Haag

James

Pombert

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

118

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“…As mechanotransductory channels, PIEZO channels form a close functional unit with the plasma membrane (43)(44)(45), also demonstrated by the inhibitory effect of GsMTx4, which acts as a gating modifier that inserts at the channel-lipid interface (32). Against this background, we decided to next test the function of dynamin, recently referred to as "membrane remodeler" (46), on PIEZO mechanotransductory function in chondrocytes.…”

Section: Resultsmentioning

confidence: 99%

Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage

Lee¹,

Leddy²,

Chen³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

348

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Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical loading. Pathological mechanical stress can lead to maladaptive cellular responses and subsequent cartilage degeneration. We sought to deconstruct chondrocyte mechanotransduction by identifying mechanosensitive ion channels functioning at injurious levels of strain. We detected robust expression of the recently identified mechanosensitive channels, PIEZO1 and PIEZO2. Combined directed expression of Piezo1 and -2 sustained potentiated mechanically induced Ca 2+ signals and electrical currents compared with single-Piezo expression. In primary articular chondrocytes, mechanically evoked Ca 2+ transients produced by atomic force microscopy were inhibited by GsMTx4, a PIEZO-blocking peptide, and by Piezo1-or Piezo2-specific siRNA. We complemented the cellular approach with an explant-cartilage injury model. GsMTx4 reduced chondrocyte death after mechanical injury, suggesting a possible therapy for reducing cartilage injury and posttraumatic osteoarthritis by attenuating Piezo-mediated cartilage mechanotransduction of injurious strains.A rticular cartilage is a hydrated connective tissue that supports loads and minimizes friction in the diarthrodial joints. It has a highly differentiated extracellular matrix (ECM) composed primarily of type II collagen, the large aggregating proteoglycan, aggrecan, and water. Chondrocytes are the only cells in cartilage and are responsible for maintaining and remodeling cartilage through a homeostatic balance of anabolic and catabolic activities. Under normal physiologic conditions, chondrocytes are exposed to millions of cycles of mechanical loading per year (1). These mechanical signals play an important role in regulating chondrocyte anabolic and biosynthetic activity, as evidenced by cartilage atrophy following periods of disuse or immobilization (2-7). However, under abnormal loading conditions (e.g., due to obesity, trauma, or joint instability), mechanical factors play a critical role in the onset and progression of osteoarthritis (1). Such "injurious" loading has been modeled in vitro using explant culture systems that replicate many of the early cellular and molecular events characteristic of osteoarthritis (8). Osteoarthritis is a painful and debilitating disease of weight-bearing joints that affects over 26 million people in the United States (9) with posttraumatic arthritis being responsible for ∼12% of the incidence of osteoarthritis (10).Despite the critical importance of mechanical loading in health and disease of synovial joints, the mechanisms of mechanotransduction of chondrocytes are not fully understood and are likely to differ under physiologic and pathologic conditions (11)(12)(13)(14). Although many different mechanisms have been shown to be involved in chondrocyte mechanotransduction (13,(15)(16)(17), recent st...

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“…Very little is known about mechanotransduction, however work on eukaryotic cells is helping to unravel the complexities of this process. For example, it is known that stretch-sensitive ion channels (Martinac 2004) and an architectural control of mechanotransduction, through a mechanochemical coupling between the cell surface and nucleus (Wang et al 2009), are key regulators of this process.…”

Section: Introductionmentioning

confidence: 99%