Targeted disruption of the<i>Lasp-1</i>gene is linked to increases in histamine-stimulated gastric HCl secretion

Chew, Catherine S.; Chen, Xunsheng; Bollag, Roni J.; Isales, Carlos M.; Ding, Ke; Zhang, Han

doi:10.1152/ajpgi.90247.2008

Cited by 27 publications

(28 citation statements)

References 42 publications

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“…5D, 5E). Lasp1, a protein expressed in gastric glands [37] has been shown to be downregulated by Sox2 in ES cells [38]. Indeed, we found that Lasp1 was barely detectable in control Sox2 loxP/lacZ gastric glands, but it was strongly upregulated in Sox2 loxP/lacZ ; Blimp1 Cre mutants (Supporting Information Fig.…”

Section: Sox2 Is Required For the Development Of Eye And Foregut Endomentioning

confidence: 73%

Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line

et al. 2013

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Sox2 is a pluripotency-conferring gene expressed in primordial germ cells (PGCs) and postnatal oocytes, but the role it plays during germ cell development and early embryogenesis is unknown. Since Sox2 ablation causes early embryonic lethality shortly after blastocyst implantation, we generated mice bearing Sox2-conditional deletion in germ cells at different stages of their development through the Cre/loxP recombination system. Embryos lacking Sox2 in PGCs show a dramatic decrease of germ cell numbers at the time of their specification. At later stages, we found that Sox2 is strictly required for PGC proliferation. On the contrary, Sox2 deletion in meiotic oocytes does not impair postnatal oogenesis and early embryogenesis, indicating that it is not essential for oocyte maturation or for zygotic development. We also show that Sox2 regulates Kit expression in PGCs and binds to discrete transcriptional regulatory sequences of this gene, which is known to be important for PGCs survival and proliferation. Sox2 also stimulates the expression of Zfp148, which is required for normal development of fetal germ cells, and Rif1, a potential regulator of PGC pluripotency.

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Section: Sox2 Is Required For the Development Of Eye And Foregut Endomentioning

confidence: 73%

Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line

et al. 2013

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“…The QTL region on GGA27 contained two genes that regulate decrease in body weight in mice, i.e., LIM and SH3 protein 1 ( LASP1 ) and phosphatidylinositol - 5 - phosphate 4 - kinase, type II, beta ( PIP4K2B ) [48, 49]. …”

Section: Resultsmentioning

confidence: 99%

Detection of QTL for traits related to adaptation to sub-optimal climatic conditions in chickens

Lien

Tixier‐Boichard

et al. 2017

Genet Sel Evol

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BackgroundGrowth traits can be used as indicators of adaptation to sub-optimal conditions. The current study aimed at identifying quantitative trait loci (QTL) that control performance under variable temperature conditions in chickens.MethodsAn F2 population was produced by crossing the Taiwan Country chicken L2 line (selected for body weight, comb area, and egg production) with an experimental line of Rhode Island Red layer R- (selected for low residual feed consumption). A total of 844 animals were genotyped with the 60 K Illumina single nucleotide polymorphism (SNP) chip. Whole-genome interval linkage mapping and a genome-wide association study (GWAS) were performed for body weight at 0, 4, 8, 12, and 16 weeks of age, shank length at 8 weeks of age, size of comb area at 16 weeks of age, and antibody response to sheep red blood cells at 11 weeks of age (7 and 14 days after primary immunization). Relevant genes were identified based on functional annotation of candidate genes and potentially relevant SNPs were detected by comparing whole-genome sequences of several birds between the parental lines.ResultsWhole-genome QTL analysis revealed 47 QTL and 714 effects associated with 178 SNPs were identified by GWAS with 5% Bonferroni genome-wide significance. Little overlap was observed between the QTL and GWAS results, with only two chromosomal regions detected by both approaches, i.e. one on GGA24 (GGA for Gallus gallus chromosome) for BW04 and one on GGAZ for six growth-related traits. Based on whole-genome sequence, differences between the parental lines based on several birds were screened in the genome-wide QTL regions and in a region detected by both methods, resulting in the identification of 106 putative candidate genes with a total of 15,443 SNPs, of which 41 were missense and 1698 were not described in the dbSNP archive.ConclusionsThe QTL detected in this study for growth and morphological traits likely influence adaptation of chickens to sub-tropical climate. Using whole-genome sequence data, we identified candidate SNPs for further confirmation of QTL in the F2 design. A strong QTL effect found on GGAZ underlines the importance of sex-linked inheritance for growth traits in chickens.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-017-0314-5) contains supplementary material, which is available to authorized users.

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“…19 The second protein band from the affinity purification comprised dynamin-1 (Q05193) and dynamin-2 (P50570), again well-known LASP-1-binding proteins. 20 Finally, the 170-kDa protein was identified as ZO-2 (Q9UDY2), a tight junction protein with nuclear-cytoplasmic distribution. 21 The results from the mass spectrometric analysis were confirmed by western blot experiments ( Figure 4a).…”

Section: Identification Of Zo-2 As a Novel Lasp-1-binding Partnermentioning

confidence: 99%

Nuclear import of LASP-1 is regulated by phosphorylation and dynamic protein–protein interactions

Mihlan¹,

Reiss²,

P³

et al. 2012

Oncogene

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LASP-1 is a multidomain protein predominantly localized at focal contacts, where it regulates cytoskeleton dynamics and cell migration. However, in different tumor entities, a nuclear LASP-1 accumulation is observed, thought to have an important role in cancer progression. Until now, the molecular mechanisms that control LASP-1 nuclear import were not elucidated. Here, we identified a novel LASP-1-binding partner, zona occludens protein 2 (ZO-2), and established its role in the signal transduction pathway of LASP-1 nucleo-cytoplasmatic shuttling. Phosphorylation of LASP-1 by PKA at serine 146 induces translocation of the LASP-1/ZO-2 complex from the cytoplasm to the nucleus. Interaction occurs within the carboxyterminal proline-rich motif of ZO-2 and the SH3 domain in LASP-1. In situ proximity ligation assay confirmed the direct binding between LASP-1 and ZO-2 and visualized the shuttling. Nuclear export is mediated by Crm-1 and a newly identified nuclear export signal in LASP-1. Finally, dephosphorylation of LASP-1 by phosphatase PP2B is suggested to relocalize the protein back to focal contacts. In summary, we define a new pathway for LASP-1 in tumor progression.

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Targeted disruption of theLasp-1gene is linked to increases in histamine-stimulated gastric HCl secretion

Cited by 27 publications

References 42 publications

Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line

Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line

Detection of QTL for traits related to adaptation to sub-optimal climatic conditions in chickens

Nuclear import of LASP-1 is regulated by phosphorylation and dynamic protein–protein interactions

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