Bmf: A Proapoptotic BH3-Only Protein Regulated by Interaction with the Myosin V Actin Motor Complex, Activated by Anoikis

The posterior determination of the Drosophila melanogaster embryo is defined by the posterior localization of oskar (osk) mRNA in the oocyte. Defects of its localization result in a lack of germ cells and failure of abdomen specification. A microtubule motor kinesin-1 is essential for osk mRNA posterior localization. Because kinesin-1 is required for two essential functions in the oocyte—transport along microtubules and cytoplasmic streaming—it is unclear how individual kinesin-1 activities contribute to the posterior determination. We examined Staufen, an RNA-binding protein that is colocalized with osk mRNA, as a proxy of posterior determination, and we used mutants that either inhibit kinesin-driven transport along microtubules or cytoplasmic streaming. We demonstrated that late-stage streaming is partially redundant with early-stage transport along microtubules for Staufen posterior localization. Additionally, an actin motor, myosin V, is required for the Staufen anchoring to the actin cortex. We propose a model whereby initial kinesin-driven transport, subsequent kinesin-driven streaming, and myosin V–based cortical retention cooperate in posterior determination.

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She3p Binds to the Rod of Yeast Myosin V and Prevents It from Dimerizing, Forming a Single-headed Motor Complex

Journal of Biological Chemistry ◽

10.1074/jbc.m708865200 ◽

2008 ◽

Vol 283 (11) ◽

pp. 6906-6914 ◽

Cited By ~ 28

Author(s):

Alex R. Hodges ◽

Elena B. Krementsova ◽

Kathleen M. Trybus

Keyword(s):

Myosin V ◽

Motor Complex

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Localization of dynein light chains 1 and 2 and their pro-apoptotic ligands

Biochemical Journal ◽

10.1042/bj20031251 ◽

2004 ◽

Vol 377 (3) ◽

pp. 597-605 ◽

Cited By ~ 51

Author(s):

Catherine L. DAY ◽

Hamsa PUTHALAKATH ◽

Gretchen SKEA ◽

Andreas STRASSER ◽

Igor BARSUKOV ◽

...

Keyword(s):

Cell Death ◽

Solution Structure ◽

Mutational Analysis ◽

Protein Structures ◽

Myosin V ◽

Dimensional Solution ◽

Binding Characteristics ◽

Motor Complex

The dynein and myosin V motor complexes are multi-protein structures that function to transport molecules and organelles within the cell. DLC (dynein light-chain) proteins, found as components of both dynein and myosin V motor complexes, connect the complexes to their cargoes. One of the roles of these motor complexes is to selectively sequester the pro-apoptotic ‘BH3-only’ (Bcl-2 homology 3-only) proteins, Bim (Bcl-2-interacting mediator of cell death) and Bmf (Bcl-2-modifying factor), and so regulate their cell death-inducing function. In vivo DLC2 is found exclusively as a component of the myosin V motor complex and Bmf binds DLC2 selectively. On the other hand, Bim interacts with DLC1 (LC8), an integral component of the dynein motor complex. The two DLCs share 93% sequence identity yet show unambiguous in vivo specificity for their respective BH3-only ligands. To investigate this specificity the three-dimensional solution structure of DLC2 was elucidated using NMR spectroscopy. In vitro structural and mutagenesis studies show that Bmf and Bim have identical binding characteristics to recombinant DLC2 or DLC1. Thus the selectivity shown by Bmf and Bim for binding DLC1 or DLC2, respectively, does not reside in their DLC-binding domains. Remarkably, mutational analysis of DLC1 and DLC2 indicates that a single surface residue (residue 41) determines the specific localization of DLCs with their respective motor complexes. These results suggest a molecular mechanism for the specific compartmentalization of DLCs and their pro-apoptotic cargoes and implicate other protein(s) in defining the specificity between the cargoes and the DLC proteins.

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Competition between kinesin-1 and myosin-V define Drosophila posterior determination

10.1101/866467 ◽

2019 ◽

Author(s):

Wen Lu ◽

Margot Lakonishok ◽

Rong Liu ◽

Neil Billington ◽

Ashley Rich ◽

...

Keyword(s):

Actin Filaments ◽

Rna Binding ◽

Cortical Microtubule ◽

Posterior Pole ◽

Myosin V ◽

Lateral Cortex ◽

Microtubule Motor ◽

Actin Motor ◽

Local Accumulation

AbstractLocal accumulation of oskar (osk) mRNA in the Drosophila oocyte determines the posterior pole of the future embryo. Two major cytoskeletal components, microtubules and actin filaments, together with a microtubule motor, kinesin-1, and an actin motor, myosin-V, are essential for osk mRNA posterior localization. In this study, we use Staufen, an RNA-binding protein that colocalizes with osk mRNA, as a proxy for posterior determination. We demonstrate that posterior localization of osk/Staufen is determined by competition between kinesin-1 and myosin-V. While kinesin-1 removes osk/Staufen from the cortex along microtubules, myosin-V anchors osk/Staufen at the cortex. Myosin-V wins over kinesin-1 at the posterior pole due to low microtubule density at this site, while kinesin-1 wins it at anterior and lateral positions because they have high density of cortically-anchored microtubules. As a result, posterior determinants are removed from the anterior and lateral cortex but retained at the posterior pole. Thus, posterior determination of Drosophila oocyte is defined by kinesin-myosin competition, whose outcome is primarily determined by cortical microtubule density.

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Competition between kinesin-1 and myosin-V defines Drosophila posterior determination

eLife ◽

10.7554/elife.54216 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 8

Author(s):

Wen Lu ◽

Margot Lakonishok ◽

Rong Liu ◽

Neil Billington ◽

Ashley Rich ◽

...

Keyword(s):

Actin Filaments ◽

Rna Binding ◽

Cortical Microtubule ◽

Posterior Pole ◽

Myosin V ◽

Lateral Cortex ◽

Microtubule Motor ◽

Actin Motor ◽

Local Accumulation

Local accumulation of oskar (osk) mRNA in the Drosophila oocyte determines the posterior pole of the future embryo. Two major cytoskeletal components, microtubules and actin filaments, together with a microtubule motor, kinesin-1, and an actin motor, myosin-V, are essential for osk mRNA posterior localization. In this study, we use Staufen, an RNA-binding protein that colocalizes with osk mRNA, as a proxy for osk mRNA. We demonstrate that posterior localization of osk/Staufen is determined by competition between kinesin-1 and myosin-V. While kinesin-1 removes osk/Staufen from the cortex along microtubules, myosin-V anchors osk/Staufen at the cortex. Myosin-V wins over kinesin-1 at the posterior pole due to low microtubule density at this site, while kinesin-1 wins at anterior and lateral positions because they have high density of cortically-anchored microtubules. As a result, posterior determinants are removed from the anterior and lateral cortex but retained at the posterior pole. Thus, posterior determination of Drosophila oocytes is defined by kinesin-myosin competition, whose outcome is primarily determined by cortical microtubule density.

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