The unconventional myosin-VIIa associates with lysosomes

Soni, Lily E.; Warren, Carmen M.; Bucci, Cecilia; Orten, Dana J.; Hasson, Tama

doi:10.1002/cm.20080

Cited by 45 publications

(34 citation statements)

References 42 publications

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“…MYO7A has been reported previously to function in the motility of RPE phagosomes , and to associate with lysosomes in an RPE cell line [Soni et al, 2005].…”

Section: Discussionmentioning

confidence: 98%

Analysis of the linkage of MYRIP and MYO7A to melanosomes by RAB27A in retinal pigment epithelial cells

Klomp

Teofilo

Legacki

et al. 2007

Cell Motil. Cytoskeleton

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The apical region of the retinal pigment epithelium (RPE) typically contains melanosomes. Their apical distribution is dependent on RAB27A and the unconventional myosin, MYO7A. Evidence from studies using in vitro binding assays, melanocyte transfection, and immunolocalization have indicated that the exophilin, MYRIP, links RAB27A on melanosomes to MYO7A, analogous to the manner that melanophilin links RAB27A on melanocyte melanosomes to MYO5A. To test the functionality of this hypothesis in RPE cells, we have examined the relationship among MYRIP, RAB27A and MYO7A with studies of RPE cells in primary culture (including live-cell imaging), analyses of mutant mouse retinas, and RPE cell fractionation experiments. Our results indicate that the retinal distribution of MYRIP is limited to the RPE, mainly the apical region. In RPE cells, RAB27A, MYRIP, and MYO7A were all associated with melanosomes, undergoing both slow and rapid movements. Analyses of mutant mice provide genetic evidence that MYRIP is linked to melanosomes via RAB27A, but show that recruitment of MYRIP to apical RPE is independent of melanosomes and RAB27A. RAB27A and MYRIP also associated with motile small vesicles of unknown origin. The present results provide evidence from live RPE cells that the RAB27A-MYRIP-MYO7A complex functions in melanosome motility. They also demonstrate that RAB27A provides an essential link to the melanosome.

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“…MYO7A has been reported previously to function in the motility of RPE phagosomes , and to associate with lysosomes in an RPE cell line [Soni et al, 2005].…”

Section: Discussionmentioning

confidence: 98%

Analysis of the linkage of MYRIP and MYO7A to melanosomes by RAB27A in retinal pigment epithelial cells

Klomp

Teofilo

Legacki

et al. 2007

Cell Motil. Cytoskeleton

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“…On the other hand, it was shown that myosin VIIA associates with melanosome via Slac-c/MyRIP and suggested that it transports melanosomes (44,45). The association of myosin VIIA with lysosomes was also reported (46). The studies described above have suggested the two potential functions of myosin VIIA, i.e.…”

Section: Actin-attached Hydrolysis Pathway (Amt-amdp)-mentioning

confidence: 90%

Drosophila Myosin VIIA Is a High Duty Ratio Motor with a Unique Kinetic Mechanism

Watanabe

Ikebe

2006

Journal of Biological Chemistry

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Mutations of myosin VIIA cause deafness in various species from human and mice to Zebrafish and Drosophila. We analyzed the kinetic mechanism of the ATPase cycle of Drosophila myosin VIIA by using a single-headed construct with the entire neck domain. The steady-state ATPase activity (0.06 s ؊1 ) was markedly activated by actin to yield V max and K ATPase of 1.72 s ؊1 and 3.2 M, respectively. The most intriguing finding is that the ATP hydrolysis predominantly takes place in the actin-bound form (actin-attached hydrolysis) for the actomyosin VIIA ATPase reaction. The ATP hydrolysis rate was much faster for the actin-attached form than the dissociated form, in contrast to other myosins reported so far. Both the ATP hydrolysis step and the phosphate release step were significantly faster than the entire ATPase cycle rate, thus not rate-determining. The rate of ADP dissociation from actomyosin VIIA was 1.86 s ؊1 , which was comparable with the overall ATPase cycle rate, thus assigned to be a rate-determining step. The results suggest that Drosophila myosin VIIA spends the majority of the ATPase cycle in an actomyosin⅐ADP form, a strong actin binding state. The duty ratio calculated from our kinetic model was ϳ0.9. Therefore, myosin VIIA is classified to be a high duty ratio motor. The present results suggested that myosin VIIA can be a processive motor to serve cargo trafficking in cells once it forms a dimer structure.Myosins are motor proteins that interact with actin filaments and convert the energy from ATP hydrolysis to produce a mechanical force. Myosins are classified based upon phylogenetic sequence comparisons of the motor domain and divided into at least 18 classes (1-3). Class VII myosins have been found in a variety of organisms from Dictyostelium and Drosophila to mammals (4 -7). There are two myosin VII genes identified in vertebrates and Drosophila, myosin VIIA and myosin VIIB. Myosin VIIA has received a great deal of interest because it was identified as a responsible gene of human Usher syndrome type 1B (USH1B) (8), and two forms of nonsyndromic deafness, DFNB2 and DFNA11 (9 -11). Quite recently, it was reported that myosin VIIA mutations lead to deafness in Drosophila (12). However, the reason why the lack of myosin VIIA causes these abnormalities is unknown, but obviously, this is due in part to the lack of knowledge regarding the myosin VIIA function at a molecular basis.The N-terminal domain of myosin VIIA is a conserved motor domain, and there are no obvious large extensions or insertions in this domain. The neck domain contains five IQ motifs that are thought to be a light chain binding site. Because calmodulin is co-purified with myosin VIIA (13), it is thought that myosin VIIA has calmodulin as its light chain subunit. The tail domain consists of a proximal segment of coiledcoil domain followed by a globular domain. Because of the presence of the coiled-coil domain, it has been assumed that myosin VIIA exists as a dimer, i.e. two-headed structure. However, there is no hard evidence showing ...

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“…Antibodies were against the following proteins: Caprin-1 (rabbit, 1:200) (Solomon et al, 2007); TIA-1 (C-20) (goat polyclonal antibody, 1:200; Santa Cruz Biotechnology); myosin VIIa (138-1) [mouse, 1:250; developed by Soni et al (Soni et al, 2005) and obtained from the Developmental Studies Hybridoma Bank (Department of Biology, University of Iowa, Iowa City, IA)]. Secondary antibodies (all Invitrogen) were used at 1:1000: goat anti-(rabbit Ig) conjugated to Alexa Fluor 488 or Alexa Fluor 546; goat anti-(mouse Ig) conjugated to Alexa Fluor 568 or Alexa 635; donkey anti-(goat Ig) conjugated to Alexa Fluor 488; and rabbit anti-(goat Ig) conjugated to Alexa Fluor 568.…”

Section: Immunofluorescence and Cochlea Slicingmentioning

confidence: 99%

Caprin-1 is a target of the deafness genePou4f3and is recruited to stress granules in cochlear hair cells in response to ototoxic damage

Towers¹,

Kelly²,

Sud³

et al. 2011

Journal of Cell Science

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The POU4 family of transcription factors are required for survival of specific cell types in different sensory systems. Pou4f3 is essential for the survival of auditory sensory hair cells and several mutations in human POU4F3 cause hearing loss. Thus, genes regulated by Pou4f3 are likely to be essential for hair cell survival. We performed a subtractive hybridisation screen in an inner-ear-derived cell line to find genes with differential expression in response to changes in Pou4f3 levels. The screen identified the stress-granule-associated protein Caprin-1 as being downregulated by Pou4f3. We demonstrated that this regulation occurs through the direct interaction of Pou4f3 with binding sites in the Caprin-1 5′ flanking sequence, and describe the expression pattern of Caprin-1 mRNA and protein in the cochlea. Moreover, we found Caprin-1-containing stress granules are induced in cochlear hair cells following aminoglycoside-induced damage. This is the first report of stress granule formation in mammalian hair cells and suggests that the formation of Caprin-1-containing stress granules is a key damage response to a clinically relevant ototoxic agent. Our results have implications for the understanding of aminoglycoside-induced hearing loss and provide further evidence that stress granule formation is a fundamental cellular stress response.

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The unconventional myosin-VIIa associates with lysosomes

Cited by 45 publications

References 42 publications

Analysis of the linkage of MYRIP and MYO7A to melanosomes by RAB27A in retinal pigment epithelial cells

Analysis of the linkage of MYRIP and MYO7A to melanosomes by RAB27A in retinal pigment epithelial cells

Drosophila Myosin VIIA Is a High Duty Ratio Motor with a Unique Kinetic Mechanism

Caprin-1 is a target of the deafness genePou4f3and is recruited to stress granules in cochlear hair cells in response to ototoxic damage

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