Rap1, Canoe and Mbt cooperate with Bazooka to promote zonula adherens assembly in the fly photoreceptor

Walther, Rhian F.; Burki, Mubarik; Pinal, Noelia; Rogerson, Clare; Pichaud, Franck

doi:10.1242/jcs.207779

Cited by 17 publications

(20 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of special interest is the involvement of Mbt and PAK4 in Cadherin-mediated cell–cell adhesion ( Faure et al, 2005 ; Pütz, 2019 ; Schneeberger and Raabe, 2003 ; Selamat et al, 2015 ; Wallace et al, 2010 ; Walther et al, 2016 ). Together with Canoe (vertebrate AF6 or AFDN), Rap1 and Bazooka (Par3), Mbt is one of the key players remodeling the zonula adherens ( Walther et al, 2018 , 2016 ). It is conceivable that this network also influences synaptic contacts, as rat AF6 localizes at synapses ( Xie et al, 2008 ) and Rap1 is involved in the development and morphogenesis of the Drosophila neuromuscular junction ( Ou et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Loss of p21-activated kinase Mbt/PAK4 causes Parkinson-like phenotypes inDrosophila

Pütz

Kram

Rauh

et al. 2021

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Parkinson's disease (PD) provokes bradykinesia, resting tremor, rigidity and postural instability but also non-motor symptoms such as depression, anxiety, sleep and cognitive impairments. Similar phenotypes can be induced in Drosophila melanogaster through modification of PD-relevant genes or the administration of PD-inducing toxins. Recent studies correlated deregulation of human p21-activated kinase PAK4 with PD, leaving open the question of a causative relationship of mutations in this gene for manifestation of PD symptoms. To figure out whether flies lacking the PAK4 homolog Mushroom bodies tiny (Mbt) show PD-like phenotypes, we tested for a variety of PD criteria. Here we demonstrate that mbt mutant flies show PD-like phenotypes including age-dependent movement deficits, reduced life expectancy and fragmented sleep. They also react to a stressful situation with higher immobility, indicating an influence of Mbt on emotional behavior. Loss of Mbt function has a negative effect on the number of dopaminergic protocerebral anterior medial (PAM) neurons, most likely caused by a proliferation defect of neural progenitors. The age-dependent movement deficits are not accompanied by a corresponding further loss of PAM neurons. Previous studies highlighted the importance of a small PAM subgroup for age-dependent PD motor impairments. We show that impaired motor skills are caused by lack of Mbt in this PAM subgroup. In addition, a broader re-expression of Mbt in PAM neurons improves life expectancy. Conversely, selective Mbt knockout in the same cells shortens life span. We conclude that mutations in Mbt/PAK4 can play a causative role in the development of Parkinson's disease phenotypes.

show abstract

Section: Discussionmentioning

confidence: 99%

Loss of p21-activated kinase Mbt/PAK4 causes Parkinson-like phenotypes inDrosophila

Pütz

Kram

Rauh

et al. 2021

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…However, as loss of Catenins prevents cell adhesion and therefore transmission of external and internal forces through the junctional network, we wanted to analyze further the role of AJs by modulating rather than abrogating AJ function. Strikingly, we found that overexpression of Afadin (Also known as Canoe, Cno) (Mandai et al, 2013;Bonello et al, 2018;Walther et al, 2018), an AJ regulator that co-localizes with β-cat to follicle cell junctions (Fig. S5B,B′), caused flattening of NCCs by stage 9 (Fig.…”

Section: Junctional Tension and Medial Myoii Levels Are Higher In Nccmentioning

confidence: 97%

Response of epithelial cell and tissue shape to external forces in vivo

2019

View full text Add to dashboard Cite

How actomyosin generates forces at epithelial adherens junctions has been extensively studied. However, less is known about how a balance between internal and external forces establishes epithelial cell, tissue and organ shape. We used the Drosophila egg chamber to investigate how contractility at adherens junctions in the follicle epithelium is modulated to accommodate and resist forces arising from the growing germ line. We found that between stages 6 and 9, adherens junction tension in the postmitotic epithelium decreases, suggesting that the junctional network relaxes to accommodate germline growth. At that time, a prominent medial Myosin II network coupled to corrugating adherens junctions develops. Local enrichment of medial Myosin II in main body follicle cells resists germline-derived forces, thus constraining apical areas and, consequently, cuboidal cell shapes at stage 9. At the tissue and organ level, local reinforcement of medial junction architecture ensures the timely contact of main body cells with the expanding oocyte and imposes circumferential constraints on the germ line guiding egg elongation. Our study provides insight into how adherens junction tension promotes cell and tissue shape transitions while integrating the growth and shape of an internally enclosed structure in vivo.

show abstract

“…Retention of Bazooka at the adherens junction plays a role in preventing the ectopic localization of the PAR complex and Ecad at the lateral membrane (Walther et al, 2016). Although the mechanisms underlying Mbt/PAK4 function during junction maturation are not fully understood, recent work in Drosophila has linked Mbt function during adherens junction maturation to that of the small GTPase Rap1 and its effector Canoe (Cno; afadin in humans), which binds to F-actin (Walther et al, 2018). The Rap1-Cno pathway also regulates Bazooka localization in the fly embryo during cellularization (Bonello et al, 2018), and Ecad trafficking in MDCK cells (Hogan et al, 2004).…”

Section: The Cdc42-pak4 Axis In Junction Maturationmentioning

confidence: 99%

Regulation of Cdc42 and its effectors in epithelial morphogenesis

Pichaud

Walther

Almeida

2019

Journal of Cell Science

Self Cite

102

View full text Add to dashboard Cite

Cdc42a member of the small Rho GTPase familyregulates cell polarity across organisms from yeast to humans. It is an essential regulator of polarized morphogenesis in epithelial cells, through coordination of apical membrane morphogenesis, lumen formation and junction maturation. In parallel, work in yeast and Caenorhabditis elegans has provided important clues as to how this molecular switch can generate and regulate polarity through localized activation or inhibition, and cytoskeleton regulation. Recent studies have revealed how important and complex these regulations can be during epithelial morphogenesis. This complexity is mirrored by the fact that Cdc42 can exert its function through many effector proteins. In epithelial cells, these include atypical PKC (aPKC, also known as PKC-3), the P21activated kinase (PAK) family, myotonic dystrophy-related Cdc42 binding kinase beta (MRCKβ, also known as CDC42BPB) and neural Wiskott-Aldrich syndrome protein (N-WASp, also known as WASL).Here, we review how the spatial regulation of Cdc42 promotes polarity and polarized morphogenesis of the plasma membrane, with a focus on the epithelial cell type.

show abstract

Rap1, Canoe and Mbt cooperate with Bazooka to promote zonula adherens assembly in the fly photoreceptor

Cited by 17 publications

References 55 publications

Loss of p21-activated kinase Mbt/PAK4 causes Parkinson-like phenotypes inDrosophila

Loss of p21-activated kinase Mbt/PAK4 causes Parkinson-like phenotypes inDrosophila

Response of epithelial cell and tissue shape to external forces in vivo

Regulation of Cdc42 and its effectors in epithelial morphogenesis

Contact Info

Product

Resources

About