The ability of a cell to detect an external chemical signal and initiate a program of directed migration along a gradient comprises the fundamental process called chemotaxis. Investigations in Dictyostelium discoideum and neutrophils have established that pleckstrin homology (PH) domain-containing proteins that bind to the PI3K products PI(3,4)P2 and PI(3,4,5)P3, such as CRAC (cytosolic regulator of adenylyl cyclase) and Akt/PKB, translocate specifically to the leading edge of chemotaxing cells. CRAC is essential for the chemoattractant-mediated activation of the adenylyl cyclase ACA, which converts ATP into cAMP, the primary chemoattractant for D. discoideum. The mechanisms by which CRAC activates ACA remain to be determined. We now show that in addition to its essential role in the activation of ACA, CRAC is involved in regulating chemotaxis. Through mutagenesis, we show that these two functions are independently regulated downstream of PI3K. A CRAC mutant that has lost the capacity to bind PI3K products does not support chemotaxis and shows minimal ACA activation. Finally, overexpression of CRAC and various CRAC mutants show strong effects on ACA activation with little effect on chemotaxis. These findings establish that chemoattractant-mediated activation of PI3K is important for the CRAC-dependent regulation of both chemotaxis and adenylyl cyclase activation.
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http://dx.doi.org/10.1016/j.cub.2005.01.007 | DOI Listing |
Cell Rep
January 2025
Department of Cell Biology and Anatomy, LSUHSC, New Orleans, LA 70112, USA; Southeast Louisiana VA Healthcare System, New Orleans, LA 70119, USA. Electronic address:
Stress can alter behavior and contributes to psychiatric disorders by regulating the expression of the GluA2 AMPA receptor subunit. We have previously shown in mice that exposure to predator odor stress elevates GluA2 transcription in cerebellar molecular layer interneurons (MLIs), and MLI activity is required for fear memory consolidation. Here, we identified the critical involvement of adenylyl cyclase 5, in both the stress-induced increase in GluA2 in MLIs and the enhancement of fear memory.
View Article and Find Full Text PDFNagoya J Med Sci
November 2024
Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Adenylate cyclase family members have recently received attention as novel therapeutic targets. However, the significance of adenylate cyclase 9 (ADCY9) in breast cancer has not been elucidated. Here, we evaluated expression in breast cancer (BC) cell lines, and polymerase chain reaction array analysis was performed to determine the correlations between expression levels and 84 tumor-associated genes.
View Article and Find Full Text PDFSheng Li Xue Bao
December 2024
College of Life Sciences, Anqing Normal University, Anqing 246133, China.
This study aimed to analyze the impact of single nucleotide polymorphism (SNP) of (encoding adenylate cyclase 3) on the outcome of high-intensity interval training (HIIT) on body composition and screen genetic markers sensitive to HIIT in Chinese Han youth. A total of 237 non-regular exercise Han college students were recruited in a 12-week HIIT program, attending sessions 3 times a week. Before and after the HIIT program, their body composition was measured.
View Article and Find Full Text PDFJ Neurosci Res
January 2025
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de Mexico, Mexico.
Lateralization of motor behavior, a common phenomenon in humans and several species, is modulated by the basal ganglia, a site pointed out for the interhemispheric differences related to lateralization. Our study aims to shed light on the potential role of the striatonigral D1 receptor in functional asymmetry in normal conditions through neurochemical and behavioral means. We found that D1 receptor activation and D1/D3 receptor coactivation in striatonigral neurons leads to more cAMP production by adenylyl cyclase in the striatum and GABA release in their terminals in the right hemisphere compared to the left.
View Article and Find Full Text PDFCell Mol Biol (Noisy-le-grand)
November 2024
Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, Academic Center for Education, Culture, and Research(ACECR), Tehran, Iran.
Breast cancer (BC) is a global health concern with a growing prevalence. Since BC is a heterogeneous cancer, transcriptome analyzes were carried out on breast tumor tissues relative to their corresponding normal tissues in order to identify gene expression signatures and perform meta-analysis. Five expression profiling by array data sets from breast tumor tissues and non-tumor neighboring tissues were retrieved following a search in the GEO database (GSE70947, GSE70905, GSE10780, GSE29044, and GSE42568).
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