An apicobasal gradient of Rac activity determines protrusion form and position

Couto, Africa; Mack, Natalie A.; Favia, Lucrezia; Georgiou, Marios

doi:10.1038/ncomms15385

Cited by 20 publications

(27 citation statements)

References 51 publications

(71 reference statements)

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“…In addition, cell polarization controls the cell cytoskeleton ( Zhu et al, 2017 ) and in particular the actin cytoskeleton that is intimately linked to the plasma membrane ( Harris, 2017 ). This occurs notably through small Rho GTPase such as RhoA, Rac1, and Cdc42 ( Mack and Georgiou, 2014 ; Couto et al, 2017 ) but also FERM proteins such as Ezrin, Radixin, Moesin ( Pelaseyed et al, 2017 ). As an example, Crb3 possess a FERM protein binding domain ( Gao et al, 2016 ).…”

Section: Epithelial Cell Polarizationmentioning

confidence: 99%

Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath Elongation

Tricaud

2018

Front. Cell. Neurosci.

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Myelin sheath geometry, encompassing myelin sheath thickness relative to internodal length, is critical to optimize nerve conduction velocity and these parameters are carefully adjusted by the myelinating cells in mammals. In the central nervous system these adjustments could regulate neuronal activities while in the peripheral nervous system they lead to the optimization and the reliability of the nerve conduction velocity. However, the physiological and cellular mechanisms that underlie myelin sheath geometry regulation are not yet fully elucidated. In peripheral nerves the myelinating Schwann cell uses several molecular mechanisms to reach and maintain the correct myelin sheath geometry, such that myelin sheath thickness and internodal length are regulated independently. One of these mechanisms is the epithelial-like cell polarization process that occurs during the early phases of the myelin biogenesis. Epithelial cell polarization factors are known to control cell size and morphology in invertebrates and mammals making these processes critical in the organogenesis. Correlative data indicate that internodal length is regulated by postnatal body growth that elongates peripheral nerves in mammals. In addition, the mechanical stretching of peripheral nerves in adult animals shows that myelin sheath length can be increased by mechanical cues. Recent results describe the important role of YAP/TAZ co-transcription factors during Schwann cell myelination and their functions have linked to the mechanotransduction through the HIPPO pathway and the epithelial polarity factor Crb3. In this review the molecular mechanisms that govern mechanically-driven myelin sheath elongation and how a Schwann cell can modulate internodal myelin sheath length, independent of internodal thickness, will be discussed regarding these recent data. In addition, the potential relevance of these mechanosensitive mechanisms in peripheral pathologies will be highlighted.

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Section: Epithelial Cell Polarizationmentioning

confidence: 99%

Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath Elongation

Tricaud

2018

Front. Cell. Neurosci.

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“…Understanding cytoneme establishment and cargo upload are now critical aspects to be determined. In turn, filopodia formation and cargo upload might be directly linked to cell polarity regulation, clearly implicating compartmentalization of cell procedures [ 99 ].…”

Section: Exosomes and Cytonemes Disseminate Hh And Wnt Proteinsmentioning

confidence: 99%

“…Basolateral polarization of filopodia formation against the apical establishment of micro-villi, and lateral lamelipodia-like protrusions, has been shown for epithelial cells [ 103 ]. This apico-basal graded distribution of protrusions is also regulated by an apico-basal concentration gradient of the Rho GTPase Rac, which is in turn defined by polarity proteins, possibly through direct inhibition of Rac activity on the apical side of the cell [ 99 , 103 ]. Experimental intervention using dominant-negative Rac in the Drosophila notum primordium affected Delta-Notch signalling through basal filopodia, essential for establishment of the highly organized bristle pattern [ 90 ].…”

Section: Transport Of Signalling Molecules In a Polarized Cellmentioning

confidence: 99%

From top to bottom: Cell polarity in Hedgehog and Wnt trafficking

et al. 2018

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Spatial organization of membrane domains within cells and cells within tissues is key to the development of organisms and the maintenance of adult tissue. Cell polarization is crucial for correct cell–cell signalling, which, in turn, promotes cell differentiation and tissue patterning. However, the mechanisms linking internal cell polarity to intercellular signalling are just beginning to be unravelled. The Hedgehog (Hh) and Wnt pathways are major directors of development and their malfunction can cause severe disorders like cancer. Here we discuss parallel advances into understanding the mechanism of Hedgehog and Wnt signal dissemination and reception. We hypothesize that cell polarization of the signal-sending and signal-receiving cells is crucial for proper signal spreading and activation of the pathway and, thus, fundamental for development of multicellular organisms.

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“…This suggests that both mechanisms are separate cellular processes. The formation and distribution of primary neurites relates to cellular polarity, in which RacGTPases (29) play a significant role, whereas the formation of ramifications yielding secondary neurites is mediated by RalGTPases via Gap-43 proteins that are associated to neuronal growth and regeneration (30).…”

Section: Discussionmentioning

confidence: 99%

Serotonin induces or inhibits neuritic regeneration of leech CNS neurons depending on neuronal identity

Vargas

Alfaro-Rodríguez

Pérez-Orive

2019

Braz J Med Biol Res

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Recovery of motor function after central nervous system (CNS) injury is dependent on the regeneration capacity of the nervous system, which is a multifactorial process influenced, among other things, by the role of neuromodulators such as serotonin. The neurotransmitter serotonin can promote neuronal regeneration but there are also reports of it causing restriction, so it is important to clarify these divergent findings in order to understand the direct scope and side effects of potential pharmacological treatments. We evaluated the effect of serotonin on the extent of neuritic outgrowth and morphology of three different neuronal types in the leech Haementeria officinalis during their regeneration in vitro: Retzius interneurons (Rz), annulus erector (AE) motoneurons, and anterolateral number 1 (AL1) CNS neurons. Neurons were isolated and cultured in L15 medium, with or without serotonin. Growth parameters were registered and quantified, and observed differences were analyzed. The addition of serotonin was found to induce AL1 neurons to increase their average growth dramatically by 8.3-fold (P=0.02; n=5), and to have no clear effect on AE motoneurons (P=0.44; n=5). For Rz interneurons, which normally do not regenerate their neurites, the addition of concanavaline-A causes substantial growth, which serotonin was found to inhibit on average by 98% (P=0.02; n=5). The number of primary neurites and their branches were also affected. These results reveal that depending on the neuronal type, serotonin can promote, inhibit, or have no effect on neuronal regeneration. This suggests that after CNS injury, non-specific pharmacological treatments affecting serotonin may have different effects on different neuronal populations.

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An apicobasal gradient of Rac activity determines protrusion form and position

Cited by 20 publications

References 51 publications

Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath Elongation

Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath Elongation

From top to bottom: Cell polarity in Hedgehog and Wnt trafficking

Serotonin induces or inhibits neuritic regeneration of leech CNS neurons depending on neuronal identity

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