PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance

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PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. / Holst, Birgitte; Madsen, Kenneth L; Jansen, Anna M; Jin, Chunyu; Rickhag, Karl Mattias; Lund, Viktor K; Jensen, Morten; Bhatia, Vikram; Sørensen, Gunnar; Madsen, Andreas N; Xue, Zhichao; Møller, Siri K; Woldbye, David; Qvortrup, Klaus; Huganir, Richard; Stamou, Dimitrios; Kjærulff, Ole; Gether, Ulrik.

In: P L o S Biology (Online), Vol. 11, No. 4, e1001542, 04.2013, p. 1-25.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Holst, B, Madsen, KL, Jansen, AM, Jin, C, Rickhag, KM, Lund, VK, Jensen, M, Bhatia, V, Sørensen, G, Madsen, AN, Xue, Z, Møller, SK, Woldbye, D, Qvortrup, K, Huganir, R, Stamou, D, Kjærulff, O & Gether, U 2013, 'PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance', P L o S Biology (Online), vol. 11, no. 4, e1001542, pp. 1-25. https://doi.org/10.1371/journal.pbio.1001542

APA

Holst, B., Madsen, K. L., Jansen, A. M., Jin, C., Rickhag, K. M., Lund, V. K., ... Gether, U. (2013). PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. P L o S Biology (Online), 11(4), 1-25. [e1001542]. https://doi.org/10.1371/journal.pbio.1001542

Vancouver

Holst B, Madsen KL, Jansen AM, Jin C, Rickhag KM, Lund VK et al. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. P L o S Biology (Online). 2013 Apr;11(4):1-25. e1001542. https://doi.org/10.1371/journal.pbio.1001542

Author

Holst, Birgitte ; Madsen, Kenneth L ; Jansen, Anna M ; Jin, Chunyu ; Rickhag, Karl Mattias ; Lund, Viktor K ; Jensen, Morten ; Bhatia, Vikram ; Sørensen, Gunnar ; Madsen, Andreas N ; Xue, Zhichao ; Møller, Siri K ; Woldbye, David ; Qvortrup, Klaus ; Huganir, Richard ; Stamou, Dimitrios ; Kjærulff, Ole ; Gether, Ulrik. / PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. In: P L o S Biology (Online). 2013 ; Vol. 11, No. 4. pp. 1-25.

Bibtex

@article{b7d53aa135334d1a84c4ffec6b14eaf8,
title = "PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance",
abstract = "Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs) domain protein PICK1 (protein interacting with C kinase 1) as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro. In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression. In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of peptidergic endocrine cells and support an important role of PICK1/ICA69 in maintenance of metabolic homeostasis.",
author = "Birgitte Holst and Madsen, {Kenneth L} and Jansen, {Anna M} and Chunyu Jin and Rickhag, {Karl Mattias} and Lund, {Viktor K} and Morten Jensen and Vikram Bhatia and Gunnar S{\o}rensen and Madsen, {Andreas N} and Zhichao Xue and M{\o}ller, {Siri K} and David Woldbye and Klaus Qvortrup and Richard Huganir and Dimitrios Stamou and Ole Kj{\ae}rulff and Ulrik Gether",
year = "2013",
month = "4",
doi = "10.1371/journal.pbio.1001542",
language = "English",
volume = "11",
pages = "1--25",
journal = "P L o S Biology (Online)",
issn = "1545-7885",
publisher = "public library of science",
number = "4",

}

RIS

TY - JOUR

T1 - PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance

AU - Holst, Birgitte

AU - Madsen, Kenneth L

AU - Jansen, Anna M

AU - Jin, Chunyu

AU - Rickhag, Karl Mattias

AU - Lund, Viktor K

AU - Jensen, Morten

AU - Bhatia, Vikram

AU - Sørensen, Gunnar

AU - Madsen, Andreas N

AU - Xue, Zhichao

AU - Møller, Siri K

AU - Woldbye, David

AU - Qvortrup, Klaus

AU - Huganir, Richard

AU - Stamou, Dimitrios

AU - Kjærulff, Ole

AU - Gether, Ulrik

PY - 2013/4

Y1 - 2013/4

N2 - Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs) domain protein PICK1 (protein interacting with C kinase 1) as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro. In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression. In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of peptidergic endocrine cells and support an important role of PICK1/ICA69 in maintenance of metabolic homeostasis.

AB - Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs) domain protein PICK1 (protein interacting with C kinase 1) as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro. In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression. In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of peptidergic endocrine cells and support an important role of PICK1/ICA69 in maintenance of metabolic homeostasis.

U2 - 10.1371/journal.pbio.1001542

DO - 10.1371/journal.pbio.1001542

M3 - Journal article

VL - 11

SP - 1

EP - 25

JO - P L o S Biology (Online)

JF - P L o S Biology (Online)

SN - 1545-7885

IS - 4

M1 - e1001542

ER -

ID: 45527701