Branched actin networks are assembled on microtubules by adenomatous polyposis coli for targeted membrane protrusion

Efimova, Nadia; Yang, Chao; Chia, Jonathan X.; Li, Ning; Lengner, Christopher J.; Neufeld, Kristi L.; Svitkina, Tatyana

doi:10.1083/jcb.202003091

Cited by 34 publications

(38 citation statements)

References 87 publications

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“…However, condensation forces can remodel actin filaments specifically at the growing microtubule plus end, whereas motor-driven forces remodel actin filaments along the microtubule lattice, or at depolymerizing microtubule ends [10, 35]. Tip-localized transport of actin filaments may be relevant given recent studies that uncovered two distinct pathways to specifically nucleate new actin filaments at the growing microtubule plus end [36, 37]. The transport mechanism identified in our study could rapidly relocate those filaments to the leading edge of the cell, where they influence the formation of new actin-based protrusions.…”

Section: Discussionmentioning

confidence: 99%

Cross-linkers at growing microtubule ends generate forces that drive actin transport

Alkemade

Wierenga

Volkov

et al. 2021

Preprint

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The actin and microtubule cytoskeletons form active networks in the cell that can contract and remodel, resulting in vital cellular processes as cell division and motility. Motor proteins play an important role in generating the forces required for these processes, but more recently the concept of passive cross-linkers being able to generate forces has emerged. So far, these passive cross-linkers have been studied in the context of separate actin and microtubule systems. Here, we show that crosslinkers also allow actin and microtubules to exert forces on each other. More specifically, we study single actin filaments that are cross-linked to growing microtubule ends, using in vitro reconstitution, computer simulations, and a minimal theoretical model. We show that microtubules can transport actin filaments over large (micrometer-range) distances, and find that this transport results from two antagonistic forces arising from the binding of cross-linkers to the overlap between the actin and microtubule filaments. The cross-linkers attempt to maximize the overlap between the actin and the tip of the growing microtubules, creating an affinity-driven forward condensation force, and simultaneously create a competing friction force along the microtubule lattice. We predict and verify experimentally how the average transport time depends on the actin filament length and the microtubule growth velocity, confirming the competition between a forward condensation force and a backward friction force. In addition, we theoretically predict and experimentally verify that the condensation force is of the order of 0.1 pN. Thus, our results reveal a new mechanism for local actin remodelling by growing microtubules.

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Section: Discussionmentioning

confidence: 99%

Cross-linkers at growing microtubule ends generate forces that drive actin transport

Alkemade

Wierenga

Volkov

et al. 2021

Preprint

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“…In fission yeast, complexes of actin and microtubule regulators (i.e., functional homologues of adenomatous polyposis coli [APC], formin, EB1, and others) present on the growing ends of microtubules promote actin polymerization to polarize cells (Chang and Martin, 2009). In neuronal growth cones and at focal adhesions, APC nucleates F-actin networks at microtubule tips (Juanes et al, 2017(Juanes et al, , 2019(Juanes et al, , 2020Efimova et al, 2020). A similar mechanism has been recapitulated in vitro with a minimal set of actin-microtubule binding proteins (Lewkowicz et al, 2008;Swiech et al, 2011;Henty-Ridilla et al, 2016).…”

Section: Coordinating Microtubule Ends and Actin Assemblymentioning

confidence: 95%

New twists in actin–microtubule interactions

Pimm

Henty-Ridilla

2021

MBoC

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Actin filaments and microtubules are cytoskeletal polymers that participate in many vital cell functions including division, morphogenesis, phagocytosis, and motility. Despite the persistent dogma that actin filament and microtubule networks are distinct in localization, structure, and function, a growing body of evidence shows that these elements are choreographed through intricate mechanisms sensitive to either polymer. Many proteins and cellular signals that mediate actin–microtubule interactions have already been identified. However, the impact of these regulators is typically assessed with actin filament or microtubule polymers alone, independent of the other system. Further, unconventional modes and regulators coordinating actin–microtubule interactions are still being discovered. Here we examine several methods of actin–microtubule crosstalk with an emphasis on the molecular links between both polymer systems and their higher-order interactions.

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“…In addition to the interaction between APC and MTs, recent evidence that APC also binds directly to actin suggests that APC could act as a regulator between MT dynamics and actin-based protrusions [ 29 ]. APC-deficient adenomas were previously shown to exhibit nondirected cell migration along the crypt-villus axis [ 30 ].…”

Section: Apc Affects Multiple Cellular Processesmentioning

confidence: 99%

Wnt-Independent and Wnt-Dependent Effects of APC Loss on the Chemotherapeutic Response

Stefanski

Prosperi

2020

IJMS

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Resistance to chemotherapy occurs through mechanisms within the epithelial tumor cells or through interactions with components of the tumor microenvironment (TME). Chemoresistance and the development of recurrent tumors are two of the leading factors of cancer-related deaths. The Adenomatous Polyposis Coli (APC) tumor suppressor is lost in many different cancers, including colorectal, breast, and prostate cancer, and its loss correlates with a decreased overall survival in cancer patients. While APC is commonly known for its role as a negative regulator of the WNT pathway, APC has numerous binding partners and functional roles. Through APC’s interactions with DNA repair proteins, DNA replication proteins, tubulin, and other components, recent evidence has shown that APC regulates the chemotherapy response in cancer cells. In this review article, we provide an overview of some of the cellular processes in which APC participates and how they impact chemoresistance through both epithelial- and TME-derived mechanisms.

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Branched actin networks are assembled on microtubules by adenomatous polyposis coli for targeted membrane protrusion

Cited by 34 publications

References 87 publications

Cross-linkers at growing microtubule ends generate forces that drive actin transport

Cross-linkers at growing microtubule ends generate forces that drive actin transport

New twists in actin–microtubule interactions

Wnt-Independent and Wnt-Dependent Effects of APC Loss on the Chemotherapeutic Response

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