scholarly journals Dynein, microtubule and cargo: a ménage à trois

2013 ◽  
Vol 41 (6) ◽  
pp. 1731-1735 ◽  
Author(s):  
Nenad Pavin ◽  
Iva M. Tolić-Nørrelykke
Keyword(s):  
Mitotic Spindle ◽  
Cytoplasmic Dynein ◽  
The Other ◽  
General Question ◽  
Cell Cortex ◽  
Cellular Functions ◽  
Binding Partners ◽  
Pulling Force ◽  
Mitosis And Meiosis ◽  
Chromosome Movements

To exert forces, motor proteins bind with one end to cytoskeletal filaments, such as microtubules and actin, and with the other end to the cell cortex, a vesicle or another motor. A general question is how motors search for sites in the cell where both motor ends can bind to their respective binding partners. In the present review, we focus on cytoplasmic dynein, which is required for a myriad of cellular functions in interphase, mitosis and meiosis, ranging from transport of organelles and functioning of the mitotic spindle to chromosome movements in meiotic prophase. We discuss how dynein targets sites where it can exert a pulling force on the microtubule to transport cargo inside the cell.

scholarly journals Mitochondria-driven assembly of a cortical anchor for mitochondria and dynein

2017 ◽  
Vol 216 (10) ◽  
pp. 3061-3071 ◽  
Author(s):  
Lauren M. Kraft ◽  
Laura L. Lackner
Keyword(s):  
Plasma Membrane ◽  
Mitotic Spindle ◽  
Cell Cortex ◽  
Dual Function ◽  
Mitochondrial Inheritance ◽  
Cellular Functions ◽  
Core Component ◽  
Spindle Positioning ◽  
The Core ◽  
Contact Sites

Interorganelle contacts facilitate communication between organelles and impact fundamental cellular functions. In this study, we examine the assembly of the MECA (mitochondria–endoplasmic reticulum [ER]–cortex anchor), which tethers mitochondria to the ER and plasma membrane. We find that the assembly of Num1, the core component of MECA, requires mitochondria. Once assembled, Num1 clusters persistently anchor mitochondria to the cell cortex. Num1 clusters also function to anchor dynein to the plasma membrane, where dynein captures and walks along astral microtubules to help orient the mitotic spindle. We find that dynein is anchored by Num1 clusters that have been assembled by mitochondria. When mitochondrial inheritance is inhibited, Num1 clusters are not assembled in the bud, and defects in dynein-mediated spindle positioning are observed. The mitochondria-dependent assembly of a dual-function cortical anchor provides a mechanism to integrate the positioning and inheritance of the two essential organelles and expands the function of organelle contact sites.

scholarly journals Overexpression of Mdm36 reveals Num1 foci that mediate dynein-dependent microtubule sliding in budding yeast

2020 ◽  
Author(s):  
Safia Omer ◽  
Katia Brock ◽  
John Beckford ◽  
Wei-Lih Lee
Keyword(s):  
Budding Yeast ◽  
Current Model ◽  
Cytoplasmic Dynein ◽  
Cell Cortex ◽  
Direct Imaging ◽  
Spindle Positioning ◽  
Sliding Mechanism ◽  
Pulling Forces ◽  
Pulling Force

ABSTRACTCurrent model for spindle positioning requires attachment of the microtubule (MT) motor cytoplasmic dynein to the cell cortex, where it generates pulling force on astral MTs to effect spindle displacement. How dynein is anchored by cortical attachment machinery to generate large spindle-pulling forces remains unclear. Here, we show that cortical clustering of Num1, the yeast dynein attachment molecule, is limited by Mdm36. Overexpression of Mdm36 results in an overall enhancement of Num1 clustering but reveals a population of dim Num1 clusters that mediate dynein-anchoring at the cell cortex. Direct imaging shows that bud-localized, dim Num1 clusters containing only ∼6 copies of Num1 molecules mediate dynein-dependent spindle pulling via lateral MT sliding mechanism. Mutations affecting Num1 clustering interfere with mitochondrial tethering but not dynein-based spindle-pulling function of Num1. We propose that formation of small ensembles of attachment molecules is sufficient for dynein anchorage and cortical generation of large spindle-pulling force.

scholarly journals Dynein light chain 1 and a spindle-associated adaptor promote dynein asymmetry and spindle orientation

2012 ◽  
Vol 198 (6) ◽  
pp. 1039-1054 ◽  
Author(s):  
Anja K. Dunsch ◽  
Dean Hammond ◽  
Jennifer Lloyd ◽  
Lothar Schermelleh ◽  
Ulrike Gruneberg ◽  
...  
Keyword(s):  
Light Chain ◽  
Mitotic Spindle ◽  
Regulatory System ◽  
Cytoplasmic Dynein ◽  
Spindle Orientation ◽  
Growth Surface ◽  
Cell Cortex ◽  
Dynein Light Chain ◽  
Dynein Motor ◽  
Pulling Forces

The cytoplasmic dynein motor generates pulling forces to center and orient the mitotic spindle within the cell. During this positioning process, dynein oscillates from one pole of the cell cortex to the other but only accumulates at the pole farthest from the spindle. Here, we show that dynein light chain 1 (DYNLL1) is required for this asymmetric cortical localization of dynein and has a specific function defining spindle orientation. DYNLL1 interacted with a spindle-microtubule–associated adaptor formed by CHICA and HMMR via TQT motifs in CHICA. In cells depleted of CHICA or HMMR, the mitotic spindle failed to orient correctly in relation to the growth surface. Furthermore, CHICA TQT motif mutants localized to the mitotic spindle but failed to recruit DYNLL1 to spindle microtubules and did not correct the spindle orientation or dynein localization defects. These findings support a model where DYNLL1 and CHICA-HMMR form part of the regulatory system feeding back spindle position to dynein at the cell cortex.

scholarly journals Overexpression of Mdm36 reveals Num1 foci that mediate dynein-dependent microtubule sliding in budding yeast

2020 ◽  
Vol 133 (20) ◽  
pp. jcs246363 ◽  
Author(s):  
Safia Omer ◽  
Katia Brock ◽  
John Beckford ◽  
Wei-Lih Lee
Keyword(s):  
Budding Yeast ◽  
Current Model ◽  
Cytoplasmic Dynein ◽  
Cell Cortex ◽  
Direct Imaging ◽  
Spindle Positioning ◽  
Sliding Mechanism ◽  
Pulling Forces ◽  
Assembly Factor ◽  
Pulling Force

ABSTRACTThe current model for spindle positioning requires attachment of the microtubule (MT) motor cytoplasmic dynein to the cell cortex, where it generates pulling force on astral MTs to effect spindle displacement. How dynein is anchored by cortical attachment machinery to generate large spindle-pulling forces remains unclear. Here, we show that cortical clustering of Num1, the yeast dynein attachment molecule, is limited by its assembly factor Mdm36. Overexpression of Mdm36 results in an overall enhancement of Num1 clustering but reveals a population of dim Num1 clusters that mediate dynein anchoring at the cell cortex. Direct imaging shows that bud-localized, dim Num1 clusters containing around only six Num1 molecules mediate dynein-dependent spindle pulling via a lateral MT sliding mechanism. Mutations affecting Num1 clustering interfere with mitochondrial tethering but do not interfere with the dynein-based spindle-pulling function of Num1. We propose that formation of small ensembles of attachment molecules is sufficient for dynein anchorage and cortical generation of large spindle-pulling forces.This article has an associated First Person interview with the first author of the paper.

scholarly journals Tumor suppressor APC is an attenuator of spindle-pulling forces during C. elegans asymmetric cell division

2018 ◽  
Vol 115 (5) ◽  
pp. E954-E963 ◽  
Author(s):  
Kenji Sugioka ◽  
Lars-Eric Fielmich ◽  
Kota Mizumoto ◽  
Bruce Bowerman ◽  
Sander van den Heuvel ◽  
...  
Keyword(s):  
Cell Division ◽  
Tumor Suppressor ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Cell Cortex ◽  
Dependent Manner ◽  
C Elegans ◽  
Pulling Forces ◽  
Underlying Mechanisms ◽  
Pulling Force

The adenomatous polyposis coli (APC) tumor suppressor has dual functions in Wnt/β-catenin signaling and accurate chromosome segregation and is frequently mutated in colorectal cancers. Although APC contributes to proper cell division, the underlying mechanisms remain poorly understood. Here we show that Caenorhabditis elegans APR-1/APC is an attenuator of the pulling forces acting on the mitotic spindle. During asymmetric cell division of the C. elegans zygote, a LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate pulling forces on astral microtubules that position the mitotic spindle. We found that APR-1 localizes to the anterior cell cortex in a Par–aPKC polarity-dependent manner and suppresses anterior centrosome movements. Our combined cell biological and mathematical analyses support the conclusion that cortical APR-1 reduces force generation by stabilizing microtubule plus-ends at the cell cortex. Furthermore, APR-1 functions in coordination with LIN-5 phosphorylation to attenuate spindle-pulling forces. Our results document a physical basis for the attenuation of spindle-pulling force, which may be generally used in asymmetric cell division and, when disrupted, potentially contributes to division defects in cancer.

scholarly journals Structure, Expression, and Function of ICAM-5

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Heping Yang
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Synapse Formation ◽  
The Other ◽  
Intercellular Adhesion Molecule ◽  
Cellular Functions ◽  
Binding Partners ◽  
The Central Nervous System ◽  
And Function

Cell adhesion is of utmost importance in normal development and cellular functions. ICAM-5 (intercellular adhesion molecule-5, telencephalin, TLN) is a member of the ICAM family of adhesion proteins. As a novel cell adhesion molecule, ICAM-5 shares many structural similarities with the other members of IgSF, especially the ICAM subgroup; however, ICAM-5 has several unique properties compared to the other ICAMs. With its nine extracellular Ig domains, ICAM-5 is the largest member of ICAM subgroup identified so far. Therefore, it is much more complex than the other ICAMs. The expression of ICAM-5 is confined to the telencephalic neurons of the central nervous system whereas all the other ICAM members are expressed mostly by cells in the immune and blood systems. The developmental appearance of ICAM-5 parallels the time of dendritic elongation and branching, and synapse formation in the telencephalon. As a somatodendrite-specific adhesion molecule, ICAM-5 not only participates in immune-nervous system interactions, it could also participate in neuronal activity, Dendrites’ targeting signals, and cognition. It would not be surprising if future investigations reveal more binding partners and other related functions of ICAM-5.

scholarly journals The tumor suppressor APC is an attenuator of spindle-pulling forces during C. elegans asymmetric cell division

2017 ◽  
Author(s):  
Kenji Sugioka ◽  
Lars-Eric Fielmich ◽  
Kota Mizumoto ◽  
Bruce Bowerman ◽  
Sander van den Heuvel ◽  
...  
Keyword(s):  
Cell Division ◽  
Mitotic Spindle ◽  
Asymmetric Cell Division ◽  
Cell Cortex ◽  
Colorectal Cancers ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
C Elegans ◽  
Pulling Forces ◽  
Pulling Force

AbstractThe adenomatous polyposis coli (APC) tumor suppressor has dual functions in Wnt/ß-catenin signaling and accurate chromosome segregation, and is frequently mutated in colorectal cancers. Although APC contributes to proper cell division, the underlying mechanisms remain poorly understood. Here we show that C. elegans APR-1/APC is an attenuator of the pulling forces acting on the mitotic spindle. During asymmetric cell division of the C. elegans zygote, a LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate pulling forces on astral microtubules that position the mitotic spindle. We found that APR-1 localizes to the anterior cell cortex in a Par-aPKC polarity-dependent manner and suppresses anterior centrosome movements. Our combined cell biological and mathematical analyses support the conclusion that cortical APR-1 reduces force generation by stabilizing microtubule plus ends at the cell cortex. Furthermore, APR-1 functions in coordination with LIN-5 phosphorylation to attenuate spindle pulling forces. Our results document a physical basis for spindle-pulling force attenuation, which may be generally used in asymmetric cell division, and when disrupted potentially contributes to division defects in cancer.Significance StatementAPC (adenomatous polyposis coli) is a Wnt signaling component as well as a microtubule-associated protein, and its mutations are frequently associated with colorectal cancers in humans. Although APC stabilizes microtubules (MTs), its mechanical role during cell division is largely unknown. Here we show that APC is an attenuator of forces acting on the mitotic spindle during asymmetric cell division of the C. elegans zygote. We performed live-imaging, laser-microsurgery, and numerical simulation to show how APC suppresses spindle pulling force generation by stabilizing microtubule plus-ends and reducing microtubule catastrophe frequency at the cell cortex. Our study is the first to document a mechanical role for the APC protein, and provides a physical basis for spindle-pulling force attenuation.

scholarly journals Mechanisms of spindle positioning

2013 ◽  
Vol 200 (2) ◽  
pp. 131-140 ◽  
Author(s):  
Francis J. McNally
Keyword(s):  
Oocyte Maturation ◽  
Cytoplasmic Dynein ◽  
Cell Cortex ◽  
Meiotic Cell ◽  
Spindle Positioning ◽  
Animal Development ◽  
Cell Divisions ◽  
Spindle Poles ◽  
Pulling Force

Accurate positioning of spindles is essential for asymmetric mitotic and meiotic cell divisions that are crucial for animal development and oocyte maturation, respectively. The predominant model for spindle positioning, termed “cortical pulling,” involves attachment of the microtubule-based motor cytoplasmic dynein to the cortex, where it exerts a pulling force on microtubules that extend from the spindle poles to the cell cortex, thereby displacing the spindle. Recent studies have addressed important details of the cortical pulling mechanism and have revealed alternative mechanisms that may be used when microtubules do not extend from the spindle to the cortex.

scholarly journals Two populations of cytoplasmic dynein contribute to spindle positioning in C. elegans embryos

2017 ◽  
Vol 216 (9) ◽  
pp. 2777-2793 ◽  
Author(s):  
Ruben Schmidt ◽  
Lars-Eric Fielmich ◽  
Ilya Grigoriev ◽  
Eugene A. Katrukha ◽  
Anna Akhmanova ◽  
...  
Keyword(s):  
Cytoplasmic Dynein ◽  
Force Generation ◽  
Cell Cortex ◽  
Animal Cells ◽  
Spindle Positioning ◽  
C Elegans ◽  
Knockout Mutants ◽  
Pulling Forces ◽  
Endogenous Proteins ◽  
Pulling Force

The position of the mitotic spindle is tightly controlled in animal cells as it determines the plane and orientation of cell division. Contacts between cytoplasmic dynein and astral microtubules (MTs) at the cell cortex generate pulling forces that position the spindle. An evolutionarily conserved Gα-GPR-1/2Pins/LGN–LIN-5Mud/NuMA cortical complex interacts with dynein and is required for pulling force generation, but the dynamics of this process remain unclear. In this study, by fluorescently labeling endogenous proteins in Caenorhabditis elegans embryos, we show that dynein exists in two distinct cortical populations. One population directly depends on LIN-5, whereas the other is concentrated at MT plus ends and depends on end-binding (EB) proteins. Knockout mutants lacking all EBs are viable and fertile and display normal pulling forces and spindle positioning. However, EB protein–dependent dynein plus end tracking was found to contribute to force generation in embryos with a partially perturbed dynein function, indicating the existence of two mechanisms that together create a highly robust force-generating system.

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