Phosphorylation of MYL12 by Myosin Light Chain Kinase Regulates Cellular Shape Changes in Cochlear Hair Cells

Oya, Ryohei; Tsukamoto, Osamu; Sato, Takashi; Kato, Hisakazu; Matsuoka, Ken; Oshima, Koichiro; Kamakura, Takefumi; Ohta, Yumi; Imai, Toshio; Takashima, Seiji; Inohara, Hidenori

doi:10.1007/s10162-021-00796-1

Cited by 7 publications

(11 citation statements)

References 50 publications

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“…Cluster 1, near cluster 0 in the UMAP (A), exhibited enriched expressions of ACTA2, MYL9, MYL12A, CALD1, TPM1, TPM2, TAGLN, DSTN, SYNPO2, SPARC, and WNT5A linked to tissue development pathways and considered signature genes in stem-myofibroblastic cell populations ( Appendix Table 2). ACTA2 encodes the smooth muscle α2 actin protein in smooth muscle cells (Talele et al 2015); MYL9 and MYL12A regulate muscle contraction (Oya et al 2021; Sun et al 2020); CALD1 is responsible for tonically inhibiting the ATPase activity of myosin in smooth muscle (Gusev 2001); tropomyosin 1 and 2 (TPM1 and TPM2) regulate muscle contraction and relaxation by interacting with actin, myosin, and the troponin complex (Bai et al 2013); TAGLN is an actin cross-linking/gelling protein found in smooth muscle (Li et al 1996); DSTN is an actin-binding component protein (Liao et al 2021); and SPARC/osteonectin regulates periodontal/osteogenesis homeostasis and collagen content. Cluster 2 was defined by enriched expression for IGFBP5, TIMP3, COL3A1, DCN, IFITM3, C1R, CTSD, FTL, C1S, NUPR1, SOX4, LUM, NNMT, FTH1, CXCL12, IGFBP6, GAS5, SFRP4, and HTRA1 genes.…”

Section: Resultsmentioning

confidence: 99%

Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells

Yang,

Alves,

Miao

et al. 2023

J Dent Res

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The regeneration of periodontal, periapical, and pulpal tissues is a complex process requiring the direct involvement of cells derived from pluripotent stem cells in the periodontal ligament and dental pulp. Dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) are spatially distinct with the potential to differentiate into similar functional and phenotypic cells. We aimed to identify the cell heterogeneity of DPSCs and PDLSCs and explore the differentiation potentials of their specialized organ-specific functions using single-cell transcriptomic analysis. Our results revealed 7 distinct clusters, with cluster 3 showing the highest potential for differentiation. Clusters 0 to 2 displayed features similar to fibroblasts. The trajectory route of the cell state transition from cluster 3 to clusters 0, 1, and 2 indicated the distinct nature of cell differentiation. PDLSCs had a higher proportion of cells (78.6%) at the G1 phase, while DPSCs had a higher proportion of cells at the S and G2/M phases (36.1%), mirroring the lower cell proliferation capacity of PDLSCs than DPSCs. Our study suggested the heterogeneity of stemness across PDLSCs and DPSCs, the similarities of these 2 stem cell compartments to be potentially integrated for regenerative strategies, and the distinct features between them potentially particularized for organ-specific functions of the dental pulp and periodontal ligament for a targeted regenerative dental tissue repair and other regeneration therapies.

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Section: Resultsmentioning

confidence: 99%

Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells

Yang,

Alves,

Miao

et al. 2023

J Dent Res

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“…Although the bullfrog has been used extensively in physiological research, it has played less of a role in biochemical investigations. NM2 and RLC have been shown to occur at the apical surfaces of hair cells in rodents (Ebrahim et al, 2013; Oya et al, 2021). In the current study, we determined that frog saccular hair cells express NM2 and MYL9 at their apical surfaces and MYL12 in their hair bundles.…”

Section: Discussionmentioning

confidence: 99%

“…Both RLC and MLCK occur in distinct isoforms in various cell types; for example, the organ of Corti expresses RLCs such as MYL9 and MYL12 as well as MYLK1 (also known as smooth-muscle MLCK or smMLCK). The phosphorylation of MYL12 by MYLK1 regulates shape changes in outer hair cells (Oya et al, 2021); moreover, deletion of the gene MYLK1 in cochlear hair cells causes hearing loss (Zhu et al, 2012; Yang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…The cuticular plate is in turn stabilized by various structures. On the apical surface of a cochlear outer hair cell, the cuticular plate is surrounded by a circumferential ring of filamentous actin and non-muscle myosin II (NM2) (Ebrahim et al, 2013; Oya et al, 2021). The interaction between these proteins mediates contraction of the apical cellular surface.…”

Section: Introductionmentioning

confidence: 99%

“…Like other myosin II molecules, NM2 consists of three pairs of proteins: two molecules of a myosin heavy chain (MYH), two of an essential light chain (ELC), and two of a regulatory light chain (RLC). The activity of NM2 is regulated through phosphorylation of the RLCs by myosin light chain kinase (MLCK) (Oya et al, 2021). When activated by the binding of the Ca 2+ -calmodulin complex, MLCK phosphorylates RLC (Tsukamoto & Kitakaze, 2013), which in turn causes myosin heads to swing toward actin filaments, increases the duty ratio of myosin-actin interaction, and promotes force generation (Levine et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Influence of myosin regulatory light chain and myosin light chain kinase on hair cells of the inner ear

Oya,

Woo,

Fabella

et al. 2023

Preprint

Self Cite

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In the receptor organs of the inner ear and lateral line, sensory hair cells detect mechanical stimuli such as sounds, accelerations, and water movements. In each instance a stimulus deflects the hair bundle, a hair cell's mechanically sensitive organelle. The bundle pivots upon the cell's apical surface, which includes an actin meshwork called the cuticular plate and is surrounded by a ring of filamentous actin and non-muscle myosin II (NM2). Myosin regulatory light chain (RLC) is expressed at the apical surfaces of hair cells and RLC is additionally found in hair bundles. NM2 and the phosphorylation of RLC by myosin light chain kinase (MLCK) have earlier been shown to regulate the sizes and shapes of hair cells' apical surfaces. We have found that inhibitors of NM2 and MLCK reduce the stiffness of hair bundles from the bullfrog's sacculus. Moreover, MLCK inhibition inhibits the spontaneous oscillation of hair bundles and increases the resting open probability of transduction channels. In addition, MLCK inhibition elevates hearing thresholds in mice. We conclude that NM2 and the phosphorylation of RLC modulate slow adaptation and thereby help to set the normal operating conditions of hair bundles.

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Post-translational modifications and age-related hearing loss

et al. 2022

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Phosphorylation of MYL12 by Myosin Light Chain Kinase Regulates Cellular Shape Changes in Cochlear Hair Cells

Cited by 7 publications

References 50 publications

Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells

Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells

Influence of myosin regulatory light chain and myosin light chain kinase on hair cells of the inner ear

Post-translational modifications and age-related hearing loss

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