PICK1 and ICA69 Control Insulin Granule Trafficking and Their Deficiencies Lead to Impaired Glucose Tolerance

Cao, Mei; Mao, Zhuo; Kam, Chuen; Xiao, Nan; Cao, Xia; Shen, Chong; Cheng, Kenneth K.Y.; Xu, Aimin; Lee, Kwong-Man; Jiang, Liwen; Xia, Jun

doi:10.1371/journal.pbio.1001541

Cited by 80 publications

(129 citation statements)

References 31 publications

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“…5H-J). Moreover, consistent with previous observations in Drosophila brain (Cao et al, 2013), we found significant reduction in ICA69 levels at Drosophila NMJs in mef2-Gal4-driven PICK1 RNAi animals (control, 100.0±3.9; PICK1 RNAi, 72.1±5.3) (Fig. 5K-M).…”

Section: Synaptic Levels Of Iglur Subunits Are Tightly Regulated By Tsupporting

confidence: 92%

“…recent study has shown that ICA69 and PICK1 stability is interdependent in Drosophila brain (Cao et al, 2013). Thus, it is likely that iGluR clusters at the NMJ are regulated by levels of ICA69 and PICK1 in muscles.…”

Section: Regulation Of Glutamate Receptor Clusters By Ica69mentioning

confidence: 97%

“…PICK1 regulates synaptic iGluR and ICA69 levels at the Drosophila NMJ Expression of ICA69 and PICK1 is interdependent in adult Drosophila brain as well as in endocrine cell lines (Cao et al, 2013). PICK1 was not detectable at the NMJ synapses in Drosophila (Jansen et al, 2009).…”

Section: Synaptic Levels Of Iglur Subunits Are Tightly Regulated By Tmentioning

confidence: 99%

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Regulation of neuromuscular junction organization by Rab2 and its effector ICA69 in Drosophila

et al. 2017

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The mechanisms underlying synaptic differentiation, which involves neuronal membrane and cytoskeletal remodeling, are not completely understood. We performed a targeted RNAi-mediated screen of Drosophila BAR-domain proteins and identified islet cell autoantigen 69 kDa (ICA69) as one of the key regulators of morphological differentiation of the larval neuromuscular junction (NMJ). We show that Drosophila ICA69 colocalizes with α-Spectrin at the NMJ. The conserved N-BAR domain of ICA69 deforms liposomes in vitro. Fulllength ICA69 and the ICAC but not the N-BAR domain of ICA69 induce filopodia in cultured cells. Consistent with its cytoskeleton regulatory role, ICA69 mutants show reduced α-Spectrin immunoreactivity at the larval NMJ. Manipulating levels of ICA69 or its interactor PICK1 alters the synaptic level of ionotropic glutamate receptors (iGluRs). Moreover, reducing PICK1 or Rab2 levels phenocopies ICA69 mutation. Interestingly, Rab2 regulates not only synaptic iGluR but also ICA69 levels. Thus, our data suggest that: (1) ICA69 regulates NMJ organization through a pathway that involves PICK1 and Rab2, and (2) Rab2 functions genetically upstream of ICA69 and regulates NMJ organization and targeting/ retention of iGluRs by regulating ICA69 levels.

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Section: Synaptic Levels Of Iglur Subunits Are Tightly Regulated By Tsupporting

confidence: 92%

Section: Regulation Of Glutamate Receptor Clusters By Ica69mentioning

confidence: 97%

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Regulation of neuromuscular junction organization by Rab2 and its effector ICA69 in Drosophila

et al. 2017

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“…ICA69 also contains an N-terminal BAR domain. ICA69 forms heteromeric BAR domain dimers with PICK1 and is the major binding partner for PICK1 in the brain and pancreas (Cao et al, 2007(Cao et al, , 2013. ICA69 inhibits synaptic targeting of AMPA receptors by restricting the localization of PICK1 to dendritic shafts (Cao et al, 2007;Xu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the BAR domain complex of PICK1 and ICA69 is associated with insulin granule trafficking in pancreatic β-cells. Deficiency of PICK1 leads to abnormal trafficking of insulin granules and glucose intolerance (Cao et al, 2013;Holst et al, 2013). Moreover, this complex has also been found to promote the budding of growth hormone granules from the Golgi apparatus in the pituitary gland (Holst et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

ICA1L forms BAR-domain complexes with PICK1 and is critical for acrosome formation in spermiogenesis

Xia

Tsang

et al. 2015

Journal of Cell Science

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Mutations in the Pick1 gene cause globozoospermia, a male infertility disorder, in both mice and humans. PICK1 is crucial for vesicle trafficking, and its deficiency in sperm cells leads to abnormal vesicle trafficking from the Golgi to the acrosome. This eventually disrupts acrosome formation and leads to male infertility. Here, we identified ICA1L, which has sequence similarities to ICA69 (also known as ICA1), as a new BAR-domain binding partner of PICK1. ICA1L is expressed in testes and brain, and is the major binding partner for PICK1 in testes. ICA1L and PICK1 are highly expressed in spermatids and trafficked together at different stages of spermiogenesis. ICA1L-knockout mice were generated by CRISPRCas technology. PICK1 expression was reduced by 80% in the testes of male mice lacking ICA1L. Sperm from ICA1L-knockout mice had abnormalities in the acrosome, nucleus and mitochondrial sheath formation. Both total and mobile sperm numbers were reduced, and about half of the remaining sperm had the characteristics of globozoospermia. These defects ultimately resulted in reduced fertility of male ICA1L-knockout mice, and ICA69/ICA1L-double knockout male mice were sterile.

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Islet‐cell autoantigen 69 accelerates liver regeneration by downregulating Tgfbr1 and attenuating Tgfβ signaling in mice

et al. 2020

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Regeneration is a unique defense mechanism of liver tissue in response to functional cell loss induced by toxic chemicals or surgical resection. In this study, we found that Islet‐cell autoantigen 69 (Ica69) accelerates liver regeneration in mice. Following 70% partial hepatectomy, both Ica69 mRNA and protein are significantly upregulated in mouse hepatocytes at the early stage of liver regeneration. Compared with the wild‐type mice, Ica69‐deficient mice have more severe liver injury, delayed liver regeneration, and high surgical accidental mortality following hepatectomy. Mechanistically, Ica69 interacts with Pick1 protein to regulate Tgfbr1 protein expression and Tgfβ‐induced Smad2 phosphorylation. Our findings suggest that Ica69 in liver tissue is a new potential target for promoting liver regeneration.

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PICK1 and ICA69 Control Insulin Granule Trafficking and Their Deficiencies Lead to Impaired Glucose Tolerance

Abstract: PICK1 and ICA69, proteins containing a BAR domain, regulate the biogenesis and maturation of insulin granules in mice.

Cited by 80 publications

References 31 publications

Regulation of neuromuscular junction organization by Rab2 and its effector ICA69 in Drosophila

Regulation of neuromuscular junction organization by Rab2 and its effector ICA69 in Drosophila

ICA1L forms BAR-domain complexes with PICK1 and is critical for acrosome formation in spermiogenesis

Islet‐cell autoantigen 69 accelerates liver regeneration by downregulating Tgfbr1 and attenuating Tgfβ signaling in mice

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