Dataset Information

Developmental upregulation of an alternative form of pcp2 with reduced GDI activity.

ABSTRACT: The pcp2/L7 gene is characterized by its very cell type-specific expression restricted to cerebellar Purkinje cells and retinal bipolar neurons. Although remarkable progress as to the biochemical properties of the encoded protein has been made, knowledge on its physiological functions remains sparse. While characterizing a pcp2-driven transgenic strain, we observed the presence of a longer, so far unknown, pcp2 transcript. Different from another recently discovered splice variant, ret-pcp2, expression of this novel transcript is observed in bipolar as well as cerebellar Purkinje cells of mid-postnatal mice. The protein encoded by our novel variant appears to be less efficient in binding to Gα subunits compared to the original L7/pcp2 protein and it is also less inhibitory with respect to GTPγ binding. Its expression in the eye appears to be independent from eye opening in postnatal mice.

SUBMITTER: Barski JJ

PROVIDER: S-EPMC3939015 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Developmental upregulation of an alternative form of pcp2 with reduced GDI activity.

Barski Jaroslaw J JJ Denker Brad M BM Guan Jiazhen J Lauth Matthias M Spreafico Fabio F Fertala Andrzej A Meyer Michael M

Cerebellum (London, England) 20140401 2

The pcp2/L7 gene is characterized by its very cell type-specific expression restricted to cerebellar Purkinje cells and retinal bipolar neurons. Although remarkable progress as to the biochemical properties of the encoded protein has been made, knowledge on its physiological functions remains sparse. While characterizing a pcp2-driven transgenic strain, we observed the presence of a longer, so far unknown, pcp2 transcript. Different from another recently discovered splice variant, ret-pcp2, expr ...[more]

PMID: 24092530

Similar Datasets

Project description:Benzo[a]pyrene (BaP) is a ubiquitous environmental contaminant that is both an endocrine disruptor and a carcinogen. Aromatase (CYP19) is a key enzyme in steroidogenesis that is responsible for conversion of androgens to estrogens and thus plays a key role in steroid homeostasis. We hypothesized that some of the adverse outcomes of early developmental exposure to BaP are the result of reduced Cyp19a1b activity. Our goal was to investigate the role of estrogen homeostasis during early development and determine the role of aromatase inhibition as a relevant mechanism in BaP's developmental toxicities. One-cell zebrafish embryos were injected with a Cyp19a1b-morpholino (MO) or control-MO. Other non-injected embryos were exposed to waterborne BaP, fadrozole (a Cyp19 inhibitor), estradiol (E2), BaP + E2, Cyp19a1b MO + E2, or fadrozole + E2 for 96 hours post-fertilization (hpf). Adverse outcomes were compared between treatments, and the ability of E2 co-exposure to rescue each observed dysmorphology was assessed. BaP significantly decreased cyp19a1b gene expression in 96 hpf zebrafish larvae homogenates. Concentrations of E2 in 48 hpf larvae were significantly decreased by BaP, fadrozole and Cyp19a1b-MO. Cumulative mortality of zebrafish larvae was significantly increased following BaP or fadrozole exposure or Cyp19a1b knockdown compared to controls. E2 co-treatment rescued mortality caused by 10 μg/L BaP, 10 μg/L fadrozole, or Cyp19a1b-MO. In a treatment-blinded morphological assessment of larvae at 96 hpf, several phenotypes were negatively impacted by BaP, fadrozole, or Cyp19a1b knockdown and rescued by exogenous E2 co-treatment; these included body length, optic vesicle size, swim bladder inflation, pericardial and abdominal edema, and incidence of normal larval tail shape. Abnormal pectoral fins were caused by BaP exposure only. Uninflated swim bladders were caused by all treatments including E2 alone. Our results indicate that certain BaP-mediated adverse developmental outcomes were mechanistically in accordance with BaP-mediated Cyp19a1b inhibition.

Dataset Information

Developmental upregulation of an alternative form of pcp2 with reduced GDI activity.

Publications

Developmental upregulation of an alternative form of pcp2 with reduced GDI activity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets