Regulated Offloading of Cytoplasmic Dynein from Microtubule Plus Ends to the Cortex

Markus, Steven M.; Lee, Wei-Lih

doi:10.1016/j.devcel.2011.04.011

Cited by 98 publications

(170 citation statements)

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“…Exactly how a tail mutation would affect dynein motor function is unclear at this point. It has been postulated that the budding yeast dynein tail may interact with the motor domain in a way that the tail would be "masked" in the presence of the motor domain (78,79). Interestingly, although the dynein regulator LIS1 binds to the motor domain at AAA3/AAA4 (26), removal of the tail appears to enhance dynein-LIS1 interaction (26,31,78).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Site in the Tail of Dynein Heavy Chain Important for Dynein Function in Vivo

Qiu

Zhang

Xiang

2013

Journal of Biological Chemistry

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Background:The dynein heavy chain tail is required for subunit interactions but not for in vitro motility. Results: A dynein tail mutation affects dynein function in vivo without affecting subunit interactions. Conclusion: A site upstream of the subunit interaction sites of the dynein tail is important in vivo. Significance: This study discovers a novel site of the dynein tail critical for motor function in vivo.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel Site in the Tail of Dynein Heavy Chain Important for Dynein Function in Vivo

Qiu

Zhang

Xiang

2013

Journal of Biological Chemistry

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“…Num1, originally identified as a player in nuclear migration, serves to anchor dynein to the cell cortex, where dynein captures and walks along astral microtubules to help orient the mitotic spindle [1–7]. More recently, a role for Num1 in mitochondrial distribution and inheritance has been described [8–10].…”

Section: Introductionmentioning

confidence: 99%

The role of mitochondria in anchoring dynein to the cell cortex extends beyond clustering the anchor protein

et al. 2018

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Organelle distribution is regulated over the course of the cell cycle to ensure that each of the cells produced at the completion of division inherits a full complement of organelles. In yeast, the protein Num1 functions in the positioning and inheritance of two essential organelles, mitochondria and the nucleus. Specifically, Num1 anchors mitochondria as well as dynein to the cell cortex, and this anchoring activity is required for proper mitochondrial distribution and dynein-mediated nuclear inheritance. The assembly of Num1 into clusters at the plasma membrane is critical for both of its anchoring functions. We have previously shown that mitochondria drive the assembly of Num1 clusters and that these mitochondria-assembled Num1 clusters serve as cortical attachment sites for dynein. Here we further examine the role for mitochondria in dynein anchoring. Using a GFP-αGFP nanobody targeting system, we synthetically clustered Num1 on eisosomes to bypass the requirement for mitochondria in Num1 cluster formation. Utilizing this system, we found that mitochondria positively impact the ability of synthetically clustered Num1 to anchor dynein and support dynein function even when mitochondria are no longer required for cluster formation. Thus, the role of mitochondria in regulating dynein function extends beyond simply concentrating Num1; mitochondria likely promote an arrangement of Num1 within a cluster that is competent for dynein anchoring. This functional dependency between mitochondrial and nuclear positioning pathways likely serves as a mechanism to order and integrate major cellular organization systems over the course of the cell cycle.

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“…What are the functional consequences of spindle capture on other aspects of the spindle orientation process? Static spindle-cortex connections could allow for proper localization and/or activation of pathways that act in subsequent steps; for example, the microtubule-mediated offloading of force-generating molecules to the cortex (Markus and Lee, 2011;Pecreaux et al, 2006). Below, we discuss the regulation of a recently characterized cortical spindle-capturing complex and present a model for how it cooperates with an evolutionarily conserved force-generating complex.…”

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confidence: 99%

Molecular pathways regulating mitotic spindle orientation in animal cells

2013

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Orientation of the cell division axis is essential for the correct development and maintenance of tissue morphology, both for symmetric cell divisions and for the asymmetric distribution of fate determinants during, for example, stem cell divisions. Oriented cell division depends on the positioning of the mitotic spindle relative to an axis of polarity. Recent studies have illuminated an expanding list of spindle orientation regulators, and a molecular model for how cells couple cortical polarity with spindle positioning has begun to emerge. Here, we review both the wellestablished spindle orientation pathways and recently identified regulators, focusing on how communication between the cell cortex and the spindle is achieved, to provide a contemporary view of how positioning of the mitotic spindle occurs.Key words: Spindle, Microtubules, Oriented cell division, Polarity, Mitosis, Centrosome IntroductionAll multicellular animals are tasked with two fundamental developmental challenges: generating cellular diversity and forming three-dimensional tissues, both of which initiate from a singlecelled zygote. Cellular diversity is spawned by cell divisions yielding non-identical daughters, and tissue morphogenesis is established through the precise three-dimensional arrangement of cell divisions that form the overall architecture of the organism. Both of these essential challenges are resolved in part through oriented cell division, which regulates embryogenesis, organogenesis and cellular differentiation. Notably, oriented cell divisions, and hence asymmetric cell divisions, remain crucial throughout adulthood as well, functioning as the basis for tissue homeostasis during growth and wound repair. One primary feature of oriented cell division is the proper positioning of the mitotic spindle relative to a defined polarity axis. In principle, spindle orientation is achieved through signaling pathways that provide a molecular link between the cell cortex and spindle microtubules. These pathways are thought to elicit both static connections and dynamic forces on the spindle to achieve the desired orientation prior to cell division. Although our knowledge of the signaling molecules involved in this process and our understanding of how they each function at the molecular level remain limited, collective efforts over the years have shed light on the importance of spindle orientation to animal development and function. Moreover, emerging evidence shows an association between improper spindle orientation and a number of developmental diseases as well as tumor formation. The study of spindle orientation is therefore fundamental to both developmental biology and human disease.Over a century ago, Oscar Hertwig discovered that sea urchin embryos biased the orientation of the mitotic spindle along their long axis, which led to a model (the 'Hertwig Rule') in which cells orient divisions in response to mechanical forces (Hertwig, 1884). The Hertwig model stated that mechanical regulation was the primary determinant of spindle orien...

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Regulated Offloading of Cytoplasmic Dynein from Microtubule Plus Ends to the Cortex

Cited by 98 publications

References 50 publications

Identification of a Novel Site in the Tail of Dynein Heavy Chain Important for Dynein Function in Vivo

Identification of a Novel Site in the Tail of Dynein Heavy Chain Important for Dynein Function in Vivo

The role of mitochondria in anchoring dynein to the cell cortex extends beyond clustering the anchor protein

Molecular pathways regulating mitotic spindle orientation in animal cells

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