Clathrin heavy chain phosphorylated at T606 plays a role in proper cell division

Yabuno, Yusuke; Uchihashi, Toshihiro; Sasakura, Towa; Shimizu, Hiroyuki; Naito, Yoshiro; Fukushima, Kunio; Ota, Keisuke; Kogo, Mikihiko; Nishimura, Hiroshi; Yabuta, Norikazu

doi:10.1080/15384101.2019.1637201

Cited by 5 publications

(5 citation statements)

References 56 publications

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“…A substrate of GAK phosphorylation is ATP1a3 as demonstrated by chemical genetic identification (Lin et al, 2018) and this is necessary for cargo trafficking. Additionally, GAK has been shown to phosphorylate clathrin heavy chain and AP2 which play a role in vesicle membrane formation and cargo packaging at the cell membrane, respectively, adding further evidence to the role of GAK in the vesicular process (Korolchuk and Banting, 2002;Yabuno et al, 2019). In contrast to DNAJC6/auxilin, GAK is an essential protein during development and adulthood in mice, with GAK knockout being lethal (Lee et al, 2008).…”

Section: Dnajc6 Dnajc13 and Dnajc26mentioning

confidence: 96%

Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies

Ebanks

Lewis

2020

Front. Neurosci.

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Parkinson's disease (PD) is a common age-related neurodegenerative disorder with disabling motor symptoms and no available disease modifying treatment. The majority of the PD cases are of unknown etiology, with both genetics and environment playing important roles. Over the past 25 years, however, genetic analysis of patients with familial history of Parkinson's and, latterly, genome wide association studies (GWAS) have provided significant advances in our understanding of the causes of the disease. These genetic insights have uncovered pathways that are affected in both genetic and sporadic forms of PD. These pathways involve oxidative stress, abnormal protein homeostasis, mitochondrial dysfunction, and lysosomal defects. In addition, newly identified PD genes and GWAS nominated genes point toward synaptic changes involving vesicles. This review will highlight the genes that contribute PD risk relating to intracellular vesicle trafficking and their functional consequences. There is still much to investigate on this newly identified and converging pathway of vesicular dynamics and PD, which will aid in better understanding and suggest novel therapeutic strategies for PD patients.

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Section: Dnajc6 Dnajc13 and Dnajc26mentioning

confidence: 96%

Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies

Ebanks

Lewis

2020

Front. Neurosci.

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“…cyclin G-associated kinase (GAK) is a ubiquitously expressed serine/threonine-protein kinase that primarily localizes to the perinuclear trans-Golgi and the plasma membrane regions (22,23). GAK, which was initially identified as a direct partner of cyclin G (24), has been associated with a diverse range of biological processes, including the maintenance of centrosome maturation and cell cycle progression (25)(26)(27)(28), clathrin-mediated endocytosis (22,23,(29)(30)(31), epidermal growth factor receptor (EGFR) signaling (32) and lysosomal enzyme sorting (33). In addition, GAK has been reported as a binding partner of leucine-rich repeat kinase 2 (LRRK2) (34), which has previously been reported to control autophagy in several systems (35)(36)(37).…”

Section: Targeted Disruption Of Gak Stagnates Autophagic Flux By Disturbing Lysosomal Dynamicsmentioning

confidence: 99%

Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics

et al. 2021

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The autophagy-lysosome system allows cells to adapt to environmental changes by regulating the degradation and recycling of cellular components, and to maintain homeostasis by removing aggregated proteins and defective organelles. cyclin G-associated kinase (GAK) is involved in the regulation of clathrin-dependent endocytosis and cell cycle progression. In addition, a single nucleotide polymorphism at the GAK locus has been reported as a risk factor for Parkinson's disease. However, the roles of GAK in the autophagy-lysosome system are not completely understood, thus the present study aimed to clarify this. In the present study, under genetic disruption or chemical inhibition of GAK, analyzing autophagic flux and observing morphological changes of autophagosomes and autolysosomes revealed that GAK controlled lysosomal dynamics via actomyosin regulation, resulting in a steady progression of autophagy. GAK knockout (KO) in A549 cells impaired autophagosome-lysosome fusion and autophagic lysosome reformation, which resulted in the accumulation of enlarged autophagosomes and autolysosomes during prolonged starvation. The stagnation of autophagic flux accompanied by these phenomena was also observed with the addition of a GAK inhibitor. Furthermore, the addition of Rho-associated protein kinase (ROcK) inhibitor or ROcK1 knockdown mitigated GAK KO-mediated effects. The results suggested a vital role of GAK in controlling lysosomal dynamics via maintaining lysosomal homeostasis during autophagy.

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“…Depletion of CHC by RNAi results in multipolar spindles, and acute inactivation of clathrin by chemically induced dimerization fragments metaphase centrosomes. A more recent study has found that GAK phosphorylates CHC at the T606 site, and the phosphorylated CHC is preferentially localized to centrosomes in interphase as well as in mitosis [62].…”

Section: Mitotic Moonlighting Functions Of Endocytic Proteinsmentioning

confidence: 99%

Functional reciprocity of proteins involved in mitosis and endocytosis

et al. 2020

The FEBS Journal

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Mitosis and endocytosis are two fundamental cellular processes essential for maintaining a eukaryotic life. Mitosis partitions duplicated chromatin enveloped in the nuclear membrane into two new cells, whereas endocytosis takes in extracellular substances through membrane invagination. These two processes are spatiotemporally separated and seemingly unrelated. However, recent studies have uncovered that endocytic proteins have moonlighting functions in mitosis, and mitotic complexes manifest additional roles in endocytosis. In this review, we summarize important proteins or protein complexes that participate in both processes, compare their mechanism of action, and discuss the rationale behind this multifunctionality. We also speculate on the possible origin of the functional reciprocity from an evolutionary perspective. An introduction to mitosis and endocytic pathwaysEukaryotic cells rely on endocytosis to uptake extracellular materials and their own plasma membrane components, in order to maintain homeostasis and respond to the varying environment [1-3]; they use the process of mitosis to achieve self-duplication and cell fate specification when differentiating [1,4]. These two Abbreviations AP2, adaptor protein-2; APC/C, anaphase-promoting complex/cyclosome; CCP, clathrin-coated pit; CCV, clathrin-coated vesicle; CHC, clathrin heavy chains; ch-TOG, colonic and hepatic tumor overexpressed gene; CLC, clathrin light chain; CME, clathrin-mediated endocytosis; CPC, chromosome passenger complex;

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Clathrin heavy chain phosphorylated at T606 plays a role in proper cell division

Cited by 5 publications

References 56 publications

Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies

Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies

Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics

Functional reciprocity of proteins involved in mitosis and endocytosis

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