Inhibition of natural killer cell-mediated cytotoxicity by ML-9, a selective inhibitor of myosin light chain kinase

Ito, Masahiko; Tanabe, Fuminori; Sato, Akihiko; Ishida, Eiko; Takami, Yoshiyuki; Shigeta, Shirô

doi:10.1016/0192-0561(89)90070-2

Cited by 11 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 and not depicted). ML-9 was previously shown to have this eff ect ( 9 ). Both blebbistatin and ML-9 reduced cytotoxicity signifi cantly compared with vehicle in several independent experiments, although YTS cells were more resistant than peripheral blood NK (pNK) cells.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibition of myosin II by blebbistatin in CD4 ϩ T cells impairs cell motility, but not IS formation ( 8 ). Moreover, inhibition of myosin II with the myosin light chain kinase inhibitor ML-9 (1-[5-chloronaphthalene-1-sulfonyl]-1H-hexahydro-1,4-diazepine hydrochloride) has been shown to inhibit NK cell cytotoxicity, but not eff ector -target conjugation ( 9 ). Myosin II is also especially relevant in NK cells because the myosin IIA isoform is recruited Natural killer (NK) cell cytotoxicity involves the formation of an activating immunological synapse (IS) between the effector and target cell through which granzymes and perforin contained in lytic granules are delivered to the target cell via exocytosis.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Myosin IIA is required for cytolytic granule exocytosis in human NK cells

Andzelm¹,

Chen²,

Krzewski³

et al. 2007

J Cell Biol

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Myosin IIA is required for cytolytic granule exocytosis in human NK cells

Andzelm¹,

Chen²,

Krzewski³

et al. 2007

J Cell Biol

View full text Add to dashboard Cite

“…4E). ML-9, an inhibitor of TRPC6 channels [66] that also inhibits myosin light chain kinase [67] and furthermore inhibits store-operated Ca 2+ entry by inhibiting STIM1 recruitment [68] had a particular effect on the oscillations. ML-9 increased basal c cyt , which resulted either in the stopping of the oscillations or in oscillations with a lower frequency, but with increased Ca 2+ amplitudes and moreover, elevated basal c cyt levels (Fig.…”

Section: Pharmacological Identification Of Ca 2+ Influx Components Anmentioning

confidence: 98%

Characterization and modeling of Ca2+ oscillations in mouse primary mesothelial cells

Pecze

Schwaller

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

Brief changes in the cytosolic and intra-organellar Ca2+ concentration serve as specific signals for various physiological processes. In mesothelial cells lining the surface of internal organs and the walls of body cavities, a re-entry in the cell cycle (G0-G1 transition) evoked by serum re-administration induces long-lasting Ca2+ oscillations with a slowly decreasing frequency. Individual mesothelial cells show a wide range of different oscillatory patterns within a single, supposedly homogenous cell population. Changes in the cytoplasmic Ca2+ concentration (ccyt) show baseline oscillatory patterns i.e., discrete Ca2+ transients starting from a constant basal ccyt level. The ER Ca2+ concentration (cER) displays a sawtooth wave at a semi-depleted ER state; the minimum level is reached just briefly after the maximal value for ccyt. These oscillations depend on plasmalemmal Ca2+ influx and on the inositol trisphosphate concentration [InsP3]; the Ca2+ influx is a crucial determinant of the oscillation frequency. Partial blocking of SERCA pumps modifies the oscillation frequency in both directions, i.e. increasing it in some cells and lowering it in others. Current mathematical models for Ca2+ oscillations mostly fail to reproduce two experimentally observed phenomena: the broad range of interspike intervals and constant basal ccyt levels between two Ca2+ spikes. Here we developed a new model based on--and fitted to--Ca2+ recordings of ccyt and cER recorded in primary mouse mesothelial cells. The model allowed for explaining many features of experimentally observed Ca2+ oscillations. We consider this model to be suitable to simulate various types of InsP3 receptor-based baseline Ca2+ oscillations.

show abstract

“…Moreover, ML-9 inhibited NK-cell degranulation (data not shown), as previously reported. 40,41 Thus, recruitment of Rab27a and Munc13-4 to perforin granules was myosin-dependent. These data suggest that Rab27a and Munc13-4 association with granules is dependent on actinbased movement of proteins or subcellular compartments.…”

Section: Recruitment Of Rab27a and Munc13-4 To Lytic Granules Is Myosmentioning

confidence: 99%

Different NK cell–activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity

Wood

Meeths

Chiang

et al. 2009

Blood

View full text Add to dashboard Cite

show abstract

Inhibition of natural killer cell-mediated cytotoxicity by ML-9, a selective inhibitor of myosin light chain kinase

Cited by 11 publications

References 22 publications

Myosin IIA is required for cytolytic granule exocytosis in human NK cells

Myosin IIA is required for cytolytic granule exocytosis in human NK cells

Characterization and modeling of Ca2+ oscillations in mouse primary mesothelial cells

Different NK cell–activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity

Contact Info

Product

Resources

About