NudC regulates actin dynamics and ciliogenesis by stabilizing cofilin 1

Zhang, Cheng; Zhang, Wen; Lu, Yi; Yan, Xin; Yan, Xiumin; Zhu, Xueliang; Liu, Wei; Yang, Yuehong; Zhou, Tian

doi:10.1038/cr.2015.152

Cited by 39 publications

(52 citation statements)

References 52 publications

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“…These results are consistent with the function of NudC in mammalian cells (Zhou et al, 2003;Aumais et al, 2003). Depletion of NudC in zebrafish by morpholinos exhibited several ciliary defects, such as body curvature, pericardial edema, hydrocephalus, and defective left-right asymmetry, which are similar to that of Cas9/NudC-gRNA-treated embryos (Zhang et al, 2015). Furthermore, the cilia in NudC morphants were abnormally elongated, orientated in random directions, and beat in an uncoordinated manner.…”

Section: Physiological Significance Of Nudc Familysupporting

confidence: 76%

“…Further results show that NudC colocalizes with cofilin 1 especially at the leading edge, and influences the stability of cofilin 1 via an Hsp90-independent pathway. Knockdown of NudC promotes cilia elongation and increases the percentage of ciliated cells, which is similar to those by actin cytoskeleton disruption or cofilin 1 depletion (Zhang et al, 2015). Exogenous expression of cofilin 1 significantly suppresses the defective ciliogenesis induced by NudC depletion, but not vice versa.…”

Section: Cellular Functions Of Nudc Family Nudcsupporting

confidence: 54%

“…Additionally, NudC and NudCL were confirmed to have intrinsic chaperone activity in vitro by preventing the aggregation of both luciferase and citrate synthase (Zheng et al, 2011;Zhu et al, 2010). Recently, we found that NudC was able to form a physiological complex with cofilin 1, a key regulator of the actin cytoskeleton (Zhang et al, 2015). Depletion of NudC markedly reduces the stability of cofilin 1, possibly through the ubiquitination-proteasome pathway.…”

Section: Chaperone Activity Of Nudc Familymentioning

confidence: 99%

“…Recently, our group finds that NudC plays essential roles in regulating actin dynamics and ciliogenesis by stabilizing cofilin 1 (Zhang et al, 2015). Depletion of NudC causes the accumulation of bundled stress fibers and inhibits cell spreading and lamellipodia formation, indicating that NudC is a crucial regulator of actin dynamics.…”

Section: Cellular Functions Of Nudc Family Nudcmentioning

confidence: 99%

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Emerging roles of NudC family: from molecular regulation to clinical implications

Wang

Zhou

et al. 2016

Sci. China Life Sci.

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Nuclear distribution gene C (NudC) was first found in Aspergillus nidulans as an upstream regulator of NudF, whose mammalian homolog is Lissencephaly 1 (Lis1). NudC is conserved from fungi to mammals. Vertebrate NudC has three homologs: NudC, NudC-like protein (NudCL), and NudC-like protein 2 (NudCL2). All members of the NudC family share a conserved p23 domain, which possesses chaperone activity both in conjunction with and independently of heat shock protein 90 (Hsp90). Our group and the others found that NudC homologs were involved in cell cycle regulation by stabilizing the components of the LIS1/dynein complex. Additionally, NudC plays important roles in cell migration, ciliogenesis, thrombopoiesis, and the inflammatory response. It has been reported that NudCL is essential for the stability of the dynein intermediate chain and ciliogenesis via its interaction with the dynein 2 complex. Our data showed that NudCL2 regulates the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone. The fourth distantly related member of the NudC family, CML66, a tumor-associated antigen in human leukemia, contains a p23 domain and appears to promote oncogenesis by regulating the IGF-1R-MAPK signaling pathway. In this review, we summarize our current knowledge of the NudC family and highlight its potential clinical relevance.nuclear distribution gene C, heat shock protein 90, p23, dynein, Lissencephaly 1, cell cycle, ciliogenesis

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Section: Physiological Significance Of Nudc Familysupporting

confidence: 76%

Section: Cellular Functions Of Nudc Family Nudcsupporting

confidence: 54%

Section: Chaperone Activity Of Nudc Familymentioning

confidence: 99%

Section: Cellular Functions Of Nudc Family Nudcmentioning

confidence: 99%

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Emerging roles of NudC family: from molecular regulation to clinical implications

Wang

Zhou

et al. 2016

Sci. China Life Sci.

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“…In addition, WIPI1, WIPI2 and WIPI4 share NudC606162 as a novel partner protein. Moreover, we found that WIPI4 directly associates with ATG2 (refs 40, 43, 71, 72, 73) (via N15/D17) and that this complex also contains AMPK and ULK1 in fed conditions.…”

Section: Discussionmentioning

confidence: 99%

WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy

et al. 2017

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Autophagy is controlled by AMPK and mTOR, both of which associate with ULK1 and control the production of phosphatidylinositol 3-phosphate (PtdIns3P), a prerequisite for autophagosome formation. Here we report that WIPI3 and WIPI4 scaffold the signal control of autophagy upstream of PtdIns3P production and have a role in the PtdIns3P effector function of WIPI1-WIPI2 at nascent autophagosomes. In response to LKB1-mediated AMPK stimulation, WIPI4-ATG2 is released from a WIPI4-ATG2/AMPK-ULK1 complex and translocates to nascent autophagosomes, controlling their size, to which WIPI3, in complex with FIP200, also contributes. Upstream, WIPI3 associates with AMPK-activated TSC complex at lysosomes, regulating mTOR. Our WIPI interactome analysis reveals the scaffold functions of WIPI proteins interconnecting autophagy signal control and autophagosome formation. Our functional kinase screen uncovers a novel regulatory link between LKB1-mediated AMPK stimulation that produces a direct signal via WIPI4, and we show that the AMPK-related kinases NUAK2 and BRSK2 regulate autophagy through WIPI4.

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Cytoskeletal networks in primary cilia: Current knowledge and perspectives

Cao

Chen

et al. 2022

Journal Cellular Physiology

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Primary cilia, microtubule-based protrusions present on the surface of most mammalian cells, function as sensory organelles that monitor extracellular signals and transduce them into intracellular biochemical responses. There is renewed research interest in primary cilia due to their essential roles in development, tissue homeostasis, and human diseases. Primary cilia dysfunction causes a large spectrum of human diseases, collectively known as ciliopathies. Despite significant advances in our understanding of primary cilia, there are still no effective agents for treating ciliopathies. Primary ciliogenesis is a highly ordered process involving membrane trafficking, basal body maturation, vesicle docking and fusion, transition zone assembly, and axoneme extension, in which actin and microtubule networks play critical and multiple roles. Actin and microtubule network architecture, isotropy, and dynamics are tightly controlled by cytoskeleton-associated proteins, a growing number of which are now recognized as responsible for cilium formation and maintenance. Here we summarize the roles of actin and microtubules and their associated proteins in primary ciliogenesis and maintenance. In doing so, we highlight that targeting cytoskeleton-associated proteins may be a promising therapeutic strategy for the treatment of ciliopathies.

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NudC regulates actin dynamics and ciliogenesis by stabilizing cofilin 1

Cited by 39 publications

References 52 publications

Emerging roles of NudC family: from molecular regulation to clinical implications

Emerging roles of NudC family: from molecular regulation to clinical implications

WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy

Cytoskeletal networks in primary cilia: Current knowledge and perspectives

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