Redundant functions of I-BAR family members, IRSp53 and IRTKS, are essential for embryonic development

Chou, Amy; Sem, Kai Ping; Lam, Wei Jun; Ahmed, Sohail; Lim, Chin Yan

doi:10.1038/srep40485

Cited by 19 publications

(17 citation statements)

References 59 publications

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“…Prompted by these observations, we examined the renal architecture in the IRSp53 -KO mice. IRSp53 -KO mice have a partially penetrant mid-gestation lethality that is due to defects in placental morphogenesis, as previously reported 41 . Some 20% to 25% of these mice, however, are born fertile and devoid of gross tissue dysmorphology 8 , 42 , 43 .…”

Section: Resultssupporting

confidence: 73%

IRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules

et al. 2020

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It is unclear whether the establishment of apical–basal cell polarity during the generation of epithelial lumens requires molecules acting at the plasma membrane/actin interface. Here, we show that the I-BAR-containing IRSp53 protein controls lumen formation and the positioning of the polarity determinants aPKC and podocalyxin. Molecularly, IRSp53 acts by regulating the localization and activity of the small GTPase RAB35, and by interacting with the actin capping protein EPS8. Using correlative light and electron microscopy, we further show that IRSp53 ensures the shape and continuity of the opposing plasma membrane of two daughter cells, leading to the formation of a single apical lumen. Genetic removal of IRSp53 results in abnormal renal tubulogenesis, with altered tubular polarity and architectural organization. Thus, IRSp53 acts as a membrane curvature-sensing platform for the assembly of multi-protein complexes that control the trafficking of apical determinants and the integrity of the luminal plasma membrane.

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Section: Resultssupporting

confidence: 73%

IRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules

et al. 2020

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“…Prompted by these observations, we examined whether there might also be similar renal architectural alterations in the IRSp53-KO mice. IRSp53-KO mice have a partially penetrant mid-gestation lethality that is due to defects in placental morphogenesis, as previously reported (data not shown; and 37 ). Some 20% to 25% of these mice, however, are born fertile and devoid of gross tissue dysmorphology 12,38,39 .…”

Section: Irsp53 Is Required For Kidney Development and Morphologysupporting

confidence: 86%

IRSp53 shapes the plasma membrane and controls polarized transport at the nascent lumen during epithelial morphogenesis

Bisi

Rizvi

Marchesi

et al. 2019

Preprint

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Establishment of apical-basal cell polarity is necessary for generation of luminal and tubular structures during epithelial morphogenesis. Molecules acting at the membrane/ actin interface are expected to be crucial in governing these processes. Here, we show that the I-BAR-containing IRSp53 protein is restricted to the luminal side of epithelial cells of various glandular organs, and is specifically enriched in renal tubules in human, mice, and zebrafish. Using three-dimensional cultures of renal MDCK and intestinal Caco-2 cysts, we show that IRSp53 is recruited early after the first cell division along the forming apical

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“…The binding to small GTPases at this region has also been reported for IRTKS, a paralog of IRSp53 (Millard et al, 2007). IRSp53 and IRTKS are essential genes as their double knockouts exhibit embryonic lethality (Chou et al, 2017).…”

Section: Introductionmentioning

confidence: 77%

Involvement of I-BAR protein IRSp53 in tumor cell growth via extracellular microvesicle secretion

Sasakura

Matsubara

Furusawa

et al. 2020

Preprint

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Cellular protrusions mediated by the membrane-deforming I-BAR domain proteinIRSp53 are involved in cell migration, including metastasis. However, the role of IRSp53 in cell proliferation remains unclear. Here, we examined the role of IRSp53 in cell proliferation and found that it acts through secretion. Coculture of gingiva squamous carcinoma Ca9-22 cells and their IRSp53-knockout cells restored proliferation to parental Ca9-22 cell levels, suggesting possible secretion dependent on IRSp53. Notably, the amounts of microvesicle fraction proteins that were secreted into the culture medium were reduced in the IRSp53-knockout cells. The IRSp53-knockout cells exhibited decreased phosphorylation of mitogen-activated protein kinase, suggesting the decrease in the proliferation signals. The phosphorylation was restored by the addition of the microvesicles. In mice xenograft Ca9-22 cells, IRSp53-containing particles were secreted around the xenograft, indicating that IRSp53-dependent secretion occurs in vivo. In a tumor mice model, IRSp53 deficiency elongated lifespan. In some human cancers, the higher levels of IRSp53 mRNA expression was found to be correlated with shorter survival years. Therefore, IRSp53 is involved in tumor progression and secretion for cellular proliferation.

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Redundant functions of I-BAR family members, IRSp53 and IRTKS, are essential for embryonic development

Cited by 19 publications

References 59 publications

IRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules

IRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules

IRSp53 shapes the plasma membrane and controls polarized transport at the nascent lumen during epithelial morphogenesis

Involvement of I-BAR protein IRSp53 in tumor cell growth via extracellular microvesicle secretion

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