Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop

Quintero, Omar A.; Unrath, William C.; Stevens, Stanley M.; Manor, Uri; Kachar, Bechara; Yengo, Christopher M.

doi:10.1074/jbc.m113.511014

Cited by 30 publications

(41 citation statements)

References 54 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this kinase is also autophosphorylated on multiple sites (Kozlov et al, 2006(Kozlov et al, , 2011. Myosin IIIa, briefly mentioned in Section 4.1.2, is phosphorylated by its increased concentration (Quintero et al, 2010(Quintero et al, , 2013. However, as its concentration is increased at filopodial tips, a relatively small region, the model geometry used in Section 3 is not appropriate.…”

Section: The Modelling Can Be Adapted To Model Specific Systemsmentioning

confidence: 97%

“…Examples include Myosin IIIa (Quintero et al, 2010(Quintero et al, , 2013) (a motor protein that binds actin and localises to filopodial tips), Ataxia Telangiectasia Mutated (ATM) Kinase (Bakkenist and Kastan, 2003;Kozlov et al, 2006Kozlov et al, , 2011Goodarzi et al, 2004;Ali et al, 2004) (an enzyme that is activated by DNA double-strand breaks), and p21 Activated Kinase 2 (PAK2) (Benner et al, 1995;Tuazon et al, 1997;Zenke et al, 1999;Wu and Wang, 2003;Jung and Traugh, 2005;Wang and Wang, 2008) (a protein that responds to several stress signals). In order to model any one of these systems explicitly, it may be necessary to incorporate other reactions specific to the system in question.…”

Section: The Model May Be Extended and Adaptedmentioning

confidence: 98%

“…However, as its concentration is increased at filopodial tips, a relatively small region, the model geometry used in Section 3 is not appropriate. Also, the phosphorylation of Myosin IIIa affects its actin binding affinity (Quintero et al, 2010(Quintero et al, , 2013, and due to this its filopodial localisation, and this may have to be incorporated in a successful model.…”

Section: The Modelling Can Be Adapted To Model Specific Systemsmentioning

confidence: 99%

See 2 more Smart Citations

Some mathematical models of intermolecular autophosphorylation

Doherty

Meere

Piiroinen

2015

Journal of Theoretical Biology

View full text Add to dashboard Cite

Section: The Modelling Can Be Adapted To Model Specific Systemsmentioning

confidence: 97%

Section: The Model May Be Extended and Adaptedmentioning

confidence: 98%

Section: The Modelling Can Be Adapted To Model Specific Systemsmentioning

confidence: 99%

See 1 more Smart Citation

Some mathematical models of intermolecular autophosphorylation

Doherty

Meere

Piiroinen

2015

Journal of Theoretical Biology

View full text Add to dashboard Cite

“…The vertical black lines represent IQ motifs. MYO3A tail magnified diagram shows that the exon 30-amino acid sequence length is greater than that of combined sequences of exons [31][32][33][34] Examining the properties of the tail domain of MYO3 has improved our understanding of MYO3 motor-based transport and its interactions with cargo. We demonstrated that the conserved THD1 of MYO3 binds to both ESPN1 and ESPNL (6,26,32) (34).…”

Section: Figure 1 Diagrammatic Representation Of the Domain Structurmentioning

confidence: 99%

Impact of the Motor and Tail Domains of Class III Myosins on Regulating the Formation and Elongation of Actin Protrusions

Raval

Quintero

Weck

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Class III myosins (MYO3A and MYO3B) are proposed to function as transporters as well as length and ultrastructure regulators within stable actin-based protrusions such as stereocilia and calycal processes. MYO3A differs from MYO3B in that it contains an extended tail domain with an additional actin-binding motif. We examined how the properties of the motor and tail domains of human class III myosins impact their ability to enhance the formation and elongation of actin protrusions. Direct examination of the motor and enzymatic properties of human MYO3A and MYO3B revealed that MYO3A is a 2-fold faster motor with enhanced ATPase activity and actin affinity. A chimera in which the MYO3A tail was fused to the MYO3B motor demonstrated that motor activity correlates with formation and elongation of actin protrusions. We demonstrate that removal of individual exons (30-34) in the MYO3A tail does not prevent filopodia tip localization but abolishes the ability to enhance actin protrusion formation and elongation in COS7 cells. Interestingly, our results demonstrate that MYO3A slows filopodia dynamics and enhances filopodia lifetime in COS7 cells. We also demonstrate that MYO3A is more efficient than MYO3B at increasing formation and elongation of stable microvilli on the surface of cultured epithelial cells. We propose that the unique features of MYO3A, enhanced motor activity, and an extended tail with tail actin-binding motif, allow it to play an important role in stable actin protrusion length and ultrastructure maintenance.

show abstract

“…As has been shown, wild-type MYO3A induces filopodial actin protrusions and localizes to their tips, particularly well when its kinase domain was removed ([Salles et al, 2009] ; Fig. 3A), since its kinase activity autoregulates its motility, transport, filopodia tip accumulation rate, and actin bundle formation and stability [Quintero et al, 2010[Quintero et al, , 2013. In all our experiments, we used a construct encoding for Cherry-tagged MYO3A containing the p.Gly488Glu mutation lacking its kinase domain (Ch-MYO3A-K p.Gly488Glu) to accurately visualize the impact of the p.Gly488Glu mutation on motility and filopodia tip accumulation while eliminating any interference of autophosphorylation events on its filopodia transport rate.…”

Section: Characterization Of the Effect Of Pgly488glu Mutation On Mymentioning

confidence: 99%

MYO3A Causes Human Dominant Deafness and Interacts with Protocadherin 15-CD2 Isoform

et al. 2016

Self Cite

View full text Add to dashboard Cite

Hereditary hearing loss is characterized by both allelic and locus genetic heterogeneity. Both recessive and dominant forms of hearing loss may be caused by different mutations in the same deafness gene. In a family with post-lingual progressive non-syndromic deafness, whole exome sequencing of genomic DNA from five hearing-impaired relatives revealed a single variant, p.Gly488Glu (rs145970949:G>A) in MYO3A, co-segregating with hearing loss as an autosomal dominant trait. This amino acid change, predicted to be pathogenic, alters a highly conserved residue in the motor domain of MYO3A. The mutation severely alters the ATPase activity and motility of the protein in vitro, and the mutant protein fails to accumulate in the filopodia tips in COS7 cells. However, the mutant MYO3A was able to reach the tips of organotypic inner ear culture hair cell stereocilia, raising the possibility of a local effect on positioning of the mechano-electrical transduction (MET) complex at the stereocilia tips. To address this hypothesis, we investigated the interaction of MYO3A with the cytosolic tail of the integral tip-link protein protocadherin 15 (PCDH15), a core component of MET complex. Interestingly, we uncovered a novel interaction between MYO3A and PCDH15 shedding new light on the function of myosin IIIA at stereocilia tips.

show abstract

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop

Cited by 30 publications

References 54 publications

Some mathematical models of intermolecular autophosphorylation

Some mathematical models of intermolecular autophosphorylation

Impact of the Motor and Tail Domains of Class III Myosins on Regulating the Formation and Elongation of Actin Protrusions

MYO3A Causes Human Dominant Deafness and Interacts with Protocadherin 15-CD2 Isoform

Contact Info

Product

Resources

About