Bleb Expansion in Migrating Cells Depends on Supply of Membrane from Cell Surface Invaginations

Goudarzi, Mohammad Ali; Tarbashevich, Katsiaryna; Mildner, Karina; Begemann, Isabell; Garcia, Jamie; Paksa, Azim; Reichman-Fried, Michal; Mahabaleshwar, Harsha; Blaser, Heiko; Hartwig, Johannes; Zeuschner, Dagmar; Galic, Milos; Bagnat, Michel; Betz, Timo; Raz, Erez

doi:10.1016/j.devcel.2017.10.030

Cited by 51 publications

(52 citation statements)

References 68 publications

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“…Other cell types that migrate using blebs, such as zebrafish primordial germ cells (PGCs), rely on Rac activity to support bleb growth (Kardash et al, 2010). Bleb-based motility in PGCs also relies on Cdc42-dependent 'wrinkling' of the plasma membrane to create membrane reservoirs that can be released as blebs form and expand (Goudarzi et al, 2017). Since the Cdc42/WASP axis supports neutrophil polarity (Fritz-Laylin et al, 2017;Yang et al, 2016), it would be interesting to test whether this pathway contributes to membrane wrinkling in neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Cell confinement reveals a branched-actin independent circuit for neutrophil polarity

Graziano¹,

Town²,

Nagy³

et al. 2018

Preprint

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Migratory cells use distinct motility modes to navigate different microenvironments, but it is unclear whether these modes rely on the same core set of polarity components. To investigate this, we disrupted Arp2/3 and WAVE complex, which assemble branched actin networks that are essential for neutrophil polarity and motility in standard adherent conditions. Surprisingly, confinement rescues polarity and movement of neutrophils lacking these components, revealing a processive bleb-based protrusion program that is mechanistically distinct from the branched actin-based protrusion program but shares some of the same core components and underlying molecular logic. We further find that the restriction of protrusion growth to one site does not always respond to membrane tension directly, as previously thought, but may rely on closely linked properties such as local membrane curvature. Our work reveals a hidden circuit for neutrophil polarity and indicates that cells have distinct molecular mechanisms for polarization that dominate in different microenvironments.to produce a single protrusion ( Fig. 1A) (Diz-Muñoz et al., 2016;Houk et al., 2012;Keren et al., 2008;Sens and Plastino, 2015).While actin polymerization serves as a key ingredient in generating the positive and negative feedback loops that give rise to polarity, we lack an understanding of how specific types of actin networks provide each kind of feedback. Immune cells assemble multiple actin networks at different subcellular locations that carry out distinct functions to support migration: Arp2/3dependent assembly of branched actin networks at the leading edge contributes to cell guidance/steering and protrusion extension, while actomyosin bundles near the trailing edge provide contractile force to lift the cell rear and squeeze the cell body forward (Lämmermann and Germain, 2014;Moreau et al., 2018). Along with these functional differences, the types of actin networks immune cells and other migratory cells employ for migration vary with microenvironment (Lämmermann and Germain, 2014;Paluch et al., 2016). The role of actin dynamics in migration is complex and likely depends on the type of actin network, its subcellular location, and the extracellular environment. Existing tools to probe the role of actin networks in both the positive and negative feedback loops needed for polarity are fairly crude and have largely been based on pharmacological perturbations that target all actin polymer (Diz-Muñoz et al., 2016;Huang et al., 2013;Inoue and Meyer, 2008;Sasaki et al., 2007;Wang et al., 2002;Weiner et al., 2007;Yang et al., 2016). More surgical experiments are needed to clarify how different subcellular actin networks contribute to polarity generation under different environmental conditions. Figure 1. WAVE complex is required for neutrophil polarity and motility.A) Polarity generation depends on fast-acting, short-range positive feedback and slower-acting, long-range negative feedback. Actin assembly participates in both types of feedback, with its role in negat...

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Section: Discussionmentioning

confidence: 99%

Cell confinement reveals a branched-actin independent circuit for neutrophil polarity

Graziano¹,

Town²,

Nagy³

et al. 2018

Preprint

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“…PGC migration is regulated by transmembrane receptors that receive external chemoattractant signals, which are then translated to cytoskeletal change by effector molecules such as phospholipids and small GTPases ( Richardson and Lehmann, 2010 ; Barton et al, 2016 ). A recent study indicated that expression of a dominant-negative form of small GTPase Cdc42 in the PGC led to round cell morphology, decreased formation of the membrane invaginations, and reduced blebbing ( Goudarzi et al, 2017 ). However, the molecular mechanism underlying Cdc42 expression and regulation in PGCs was remained unclear in zebrafish.…”

Section: Introductionmentioning

confidence: 99%

Maternal miR-202-5p is required for zebrafish primordial germ cell migration by protecting small GTPase Cdc42

Jin

Liu

Xiang

et al. 2019

Journal of Molecular Cell Biology

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Abstract In many lower animals, germ cell formation, migration, and maintenance depend on maternally provided determinants in germ plasm. In zebrafish, these processes have been extensively studied in terms of RNA-binding proteins and other coding genes. The role of small non-coding RNAs in the regulation of primordial germ cell (PGC) development remains largely unknown and poorly investigated, even though growing interests for the importance of miRNAs involved in a wide variety of biological processes. Here, we reported the role and mechanism of the germ plasm-specific miRNA miR-202-5p in PGC migration: (i) both maternal loss and knockdown of miR-202-5p impaired PGC migration indicated by the mislocalization and reduced number of PGCs; (ii) cdc42se1 was a direct target gene of miR-202-5p, and overexpression of Cdc42se1 in PGCs caused PGC migration defects similar to those observed in loss of miR-202-5p mutants; (iii) Cdc42se1 not only interacted with Cdc42 but also inhibited cdc42 transcription, and overexpression of Cdc42 could rescue PGC migration defects in Cdc42se1 overexpressed embryos. Thus, miR-202-5p regulates PGC migration by directly targeting and repressing Cdc42se1 to protect the expression of Cdc42, which interacts with actin to direct PGC migration.

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“…Accumulating evidence indicate that EVs generated by highly aggressive cancer cells are capable of promoting tumor growth [47][48][49]. We showed in Fig.…”

Section: Discussionmentioning

confidence: 61%

“…One possible explanation for this is that membrane sources for blebbing are diminished upon Rab11 inhibition. Bleb inflation is the result of unfolding of stored membrane, which could originate from fusion of Rab11 vesicles with plasma membrane [46,47]. Alternatively, Rab11 inhibition may prevent cytoplasmic flow from pushing the membrane outwards.…”

Section: Discussionmentioning

confidence: 99%

Subcellular localization of glypican-5 associates with dynamic cell motility and cell communication of the human mesenchymal stem cell line U3DT

Takeuchi

Monobe

et al. 2019

Preprint

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Glypican-5 (GPC5) is a heparan sulfate proteoglycan (HSPG) localized to the plasma membrane. We previously reported that in the human mesenchymal stem cell line UE6E7T3, GPC5 is overexpressed in association with transformation and promotes cell proliferation by acting as a co-receptor for Sonic hedgehog signaling. In this study, we found using an immunofluorescence microscopy that in transformed cells (U3DT), GPC5 localized not only at primary cilia on the cell surface, but also at the leading edge of migrating cells, at the intercellular bridge and blebs during cytokinesis, and in extracellular vesicles. In each subcellular region, GPC5 colocalized with the small GTPase Rab11. These observations suggest that the colocalization of GPC5 with Rab11 is crucial for its function, and that its activity in each subcellular compartment promotes proliferation of U3DT cells. Our findings indicate that GPC5 plays active and essential roles in regulation of U3DT cell proliferation, and provides several insights into the functions of GPC5 that could be elucidated by future studies.

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Bleb Expansion in Migrating Cells Depends on Supply of Membrane from Cell Surface Invaginations

Cited by 51 publications

References 68 publications

Cell confinement reveals a branched-actin independent circuit for neutrophil polarity

Cell confinement reveals a branched-actin independent circuit for neutrophil polarity

Maternal miR-202-5p is required for zebrafish primordial germ cell migration by protecting small GTPase Cdc42

Subcellular localization of glypican-5 associates with dynamic cell motility and cell communication of the human mesenchymal stem cell line U3DT

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