The interaction between CASK and the tumour suppressor Dlg1 regulates mitotic spindle orientation in mammalian epithelia

Porter, Andrew; White, Gavin R M; Mack, Natalie A.; Malliri, Angeliki

doi:10.1242/jcs.230086

Cited by 27 publications

(24 citation statements)

References 46 publications

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“…In the Drosophila visual system, the MAGUK complex Lin-7/Dlg/CASK is involved in synaptic stabilization and the interaction between CASK and Dlg proteins has been described as direct (Soukup et al, 2013). The role of CASK in the recruitment of Dlg1 to the membrane in various cell types has been confirmed in a recent study showing that the N-terminal domain of Dlg1 is critical for its interaction with CASK (Porter et al, 2019). In mammals, the existence of the APP/X11/CASK ternary complex has also been documented (Wang et al, 2009), and the regulation of neuronal excitability through potassium Kir2 channels involves a macromolecular complex consisting of Lin-7/SAP97/CASK/X11 (Leonoudakis et al, 2004).…”

Section: Discussionmentioning

confidence: 91%

Interactions between amyloid precursor protein-like (APPL) and MAGUK scaffolding proteins contribute to appetitive long-term memory inDrosophila melanogaster

Silva

Niehage

Maglione

et al. 2020

Journal of Neurogenetics

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Amyloid precursor protein (APP), the precursor of amyloid beta peptide, plays a central role in Alzheimer's disease (AD), a pathology characterized by memory decline and synaptic loss upon aging. Understanding the physiological role of APP is fundamental in deciphering the progression of AD, and several studies suggest a synaptic function via protein-protein interactions. Nevertheless, it remains unclear whether and how these interactions contribute to memory. In Drosophila, we previously showed that APP-like (APPL), the fly APP homolog, is required for aversive associative memory in the olfactory memory center, the mushroom body (MB). In the present study, we show that APPL is required for appetitive long-term memory (LTM), another form of associative memory, in a specific neuronal subpopulation of the MB, the a'/b' Kenyon cells. Using a biochemical approach, we identify the synaptic MAGUK (membrane-associated guanylate kinase) proteins X11, CASK, Dlgh2 and Dlgh4 as interactants of the APP intracellular domain (AICD). Next, we show that the Drosophila homologs CASK and Dlg are also required for appetitive LTM in the a'/b' neurons. Finally, using a double RNAi approach, we demonstrate that genetic interactions between APPL and CASK, as well as between APPL and Dlg, are critical for appetitive LTM. In summary, our results suggest that APPL contributes to associative long-term memory through its interactions with the main synaptic scaffolding proteins CASK and Dlg. This function should be conserved across species.

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Section: Discussionmentioning

confidence: 91%

Interactions between amyloid precursor protein-like (APPL) and MAGUK scaffolding proteins contribute to appetitive long-term memory inDrosophila melanogaster

Silva

Niehage

Maglione

et al. 2020

Journal of Neurogenetics

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“…4 I). We then quantified centrosomal PLK4 intensity in this S-phase population by imaging on the Leica SP8 confocal microscope, using the hybrid detectors in their quantitative photon counting mode, similar to the method we used previously for quantitative image analysis ( Porter et al, 2019 ). Using this complementary imaging modality, we again saw that Tiam1 depletion led to an increase in centrosomal PLK4 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

The RAC1 activator Tiam1 regulates centriole duplication through controlling PLK4 levels

Porter

Reed

White

et al. 2021

Journal of Cell Science

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Centriole duplication is tightly controlled to maintain correct centriole number through the cell cycle. Key to this is the regulated degradation of PLK4, the master regulator of centriole duplication. Here we show that the Rac1 guanine nucleotide exchange factor (GEF) Tiam1 localises to centrosomes during S-phase, where it is required for maintenance of normal centriole number. Depletion of Tiam1 leads to an increase in centrosomal PLK4 and centriole overduplication, whereas overexpression of Tiam1 can restrict centriole overduplication. Ultimately Tiam1 depletion leads to lagging chromosomes at anaphase and aneuploidy, potential drivers of malignant progression. The effects of Tiam1 depletion on centrosomal PLK4 levels and centriole overduplication can be rescued by re-expression of both wild-type Tiam1 and catalytically inactive (GEF*) Tiam1, but not by Tiam1 mutants unable to bind to the F-box protein βTRCP, implying that Tiam1 regulates PLK4 levels through promoting βTRCP-mediated degradation independently of Rac1 activation.

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“…Given our finding that Scribble and E-cadherin functionally interact on retraction fibres, and the published evidence that all three members of the Scribble complex (Scribble, Discs large and Lethal Giant Larvae) mediate spindle orientation in intact tissues 40, 50, 51, 56–60 , we next investigated whether Scribble was required for spindle orientation in single cells. Indeed, in MCF10A cells lacking Scribble and undergoing cell division, the spindle was mis-oriented ( Fig.…”

Section: Resultsmentioning

confidence: 99%

A Scribble-E-cadherin complex controls daughter cell patterning by multiple mechanisms

Chann

Chen

Kinwel

et al. 2021

Preprint

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The fate of the two daughter cells is intimately connected to their positioning, which is in turn regulated by cell junction remodelling and orientation of the mitotic spindle. How multiple cues are integrated to dictate the ultimate patterning of daughters is not clear. Here, we identify novel mechanisms of regulation of daughter positioning in single MCF10A cells. The polarity protein, Scribble, links E-cadherin to NuMA and Arp2/3 signalling for sequential roles in daughter positioning. First Scribble transmits cues from E-cadherin localised in retraction fibres to control orientation of the mitotic spindle. Second, Scribble re-locates to the junction between the two daughters to allow a new E-cadherin-based-interface to form between them, influencing the width of the nascent daughter-daughter junction, generation of filopodia and subsequent cell patterning. Thus, E-cadherin and Scribble dynamically relocate to different intracellular sites during cell division to orient the mitotic spindle and control placement of the daughter cells after cell division.

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The interaction between CASK and the tumour suppressor Dlg1 regulates mitotic spindle orientation in mammalian epithelia

Cited by 27 publications

References 46 publications

Interactions between amyloid precursor protein-like (APPL) and MAGUK scaffolding proteins contribute to appetitive long-term memory inDrosophila melanogaster

Interactions between amyloid precursor protein-like (APPL) and MAGUK scaffolding proteins contribute to appetitive long-term memory inDrosophila melanogaster

The RAC1 activator Tiam1 regulates centriole duplication through controlling PLK4 levels

A Scribble-E-cadherin complex controls daughter cell patterning by multiple mechanisms

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