CACNA1D-Related Channelopathies: From Hypertension to Autism

Ortner, Nadine J.

doi:10.1007/164_2022_626

Cited by 8 publications

(3 citation statements)

References 146 publications

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“…CACNA1d is a calcium voltage-gated channel subunit located on the cell membrane, which can activate guannylic acid exchange factors such as RasGRF and RasGRPs by increasing intracellular calcium ion concentration, and participate in the activation of Ras. Further activation of MAPK signaling pathway ( Fernandez-Medarde and Santos, 2011 ; Stone, 2011 ; Xu W. et al, 2022 ; Ortner, 2023 ). tRF-Val-CAC-016 combined with CACNA1d 3 'UTR inhibited the expression of CACNA1d.…”

Section: Deciphering Mapk Signaling Pathways and Tsrnas In Cellular P...mentioning

confidence: 99%

Unveiling the role of tRNA-derived small RNAs in MAPK signaling pathway: implications for cancer and beyond

Wang,

Huang,

Ying

et al. 2024

Front. Genet.

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tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs originating from mature or precursor tRNAs (pre-tRNA), typically spanning 14 to 30 nt. The Mitogen-activated protein kinases (MAPK) pathway orchestrates cellular responses, influencing proliferation, differentiation, apoptosis, and transformation. tsRNAs influence the expression of the MAPK signaling pathway by targeting specific proteins within the pathway. Presently, four MAPK-linked tsRNAs have implications in gastric cancer (GC) and high-grade serous ovarian cancer (HGSOC). Notably, tRF-Glu-TTC-027 and tRF-Val-CAC-016 modulate MAPK-related protein expression, encompassing p38, Myc, ERK, CyclinD1, CyclinB, and c-Myc, hindering GC progression via MAPK pathway inhibition. Moreover, tRF-24-V29K9UV3IU and tRF-03357 remain unexplored in specific mechanisms. KEGG analysis posits varied tsRNAs in MAPK pathway modulation for diverse non-cancer maladies. Notably, high tRF-36-F900BY4D84KRIME and tRF-23-87R8WP9IY expression relates to varicose vein (VV) risk. Elevated tiRNA-Gly-GCC-001, tRF-Gly-GCC-012, tRF-Gly-GCC-013, and tRF-Gly-GCC-016 target spinal cord injury (SCI)-related brain-derived neurotrophic factor (BDNF), influencing MAPK expression. tRF-Gly-CCC-039 associates with diabetes foot sustained healing, while tRF-5014a inhibits autophagy-linked ATG5 in diabetic cardiomyopathy (DCM). Additionally, tsRNA-14783 influences keloid formation by regulating M2 macrophage polarization. Upregulation of tRF-Arg-ACG-007 and downregulation of tRF-Ser-GCT-008 are associated with diabetes. tsRNA-04002 alleviates Intervertebral disk degeneration (IDD) by targeting PRKCA. tsRNA-21109 alleviates Systemic lupus erythematosus (SLE) by inhibiting macrophage M1 polarization. The upregulated tiNA-Gly-GCC-002 and the downregulated tRF-Ala-AGC-010, tRF-Gln-CTG-005 and tRF-Leu-AAG-001 may be involved in the pathogenesis of Lupus nephritis (LN) by affecting the expression of MAPK pathway. Downregulation of tsRNA-1018, tsRNA-3045b, tsRNA-5021a and tsRNA-1020 affected the expression of MAPK pathway, thereby improving Acute lung injury (ALI). This review comprehensively dissects tsRNA roles in MAPK signaling across cancers and other diseases, illuminating a novel avenue for translational medical exploration.

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Section: Deciphering Mapk Signaling Pathways and Tsrnas In Cellular P...mentioning

confidence: 99%

Unveiling the role of tRNA-derived small RNAs in MAPK signaling pathway: implications for cancer and beyond

Wang,

Huang,

Ying

et al. 2024

Front. Genet.

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“…In cardiac musculature, Ca v 1.3 is involved in pacemaking and AV conduction of the heart ( Mesirca et al, 2016b ). Ca v 1.3 −/− mice are deaf and exhibit bradycardia and arrhythmia resulting from sinoatrial (SA) node dysfunction ( Platzer et al, 2000 ; Ortner, 2023 ). This is likely because of the crucial role that Ca v 1.3 channels play in the diastolic depolarization of SA node pacemaker cells ( Mangoni et al, 2003 ).…”

Section: Functional Role Of Ca V 13 In the Heartmentioning

confidence: 99%

Pathophysiology of Cav1.3 L-type calcium channels in the heart

Zaveri

Srivastava

et al. 2023

Front. Physiol.

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Ca2+ plays a crucial role in excitation-contraction coupling in cardiac myocytes. Dysfunctional Ca2+ regulation alters the force of contraction and causes cardiac arrhythmias. Ca2+ entry into cardiomyocytes is mediated mainly through L-type Ca2+ channels, leading to the subsequent Ca2+ release from the sarcoplasmic reticulum. L-type Ca2+ channels are composed of the conventional Cav1.2, ubiquitously expressed in all heart chambers, and the developmentally regulated Cav1.3, exclusively expressed in the atria, sinoatrial node, and atrioventricular node in the adult heart. As such, Cav1.3 is implicated in the pathogenesis of sinoatrial and atrioventricular node dysfunction as well as atrial fibrillation. More recently, Cav1.3 de novo expression was suggested in heart failure. Here, we review the functional role, expression levels, and regulation of Cav1.3 in the heart, including in the context of cardiac diseases. We believe that the elucidation of the functional and molecular pathways regulating Cav1.3 in the heart will assist in developing novel targeted therapeutic interventions for the aforementioned arrhythmias.

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“…These disease-linked mutations have direct effects on channel gating and are believed to underlie the observed ASD-associated phenotypes. We direct readers to the excellent reviews by Ortner et al 2020 [ 12 ] and Ortner 2023 [ 13 ] on Ca v 1.3 mutations and their impact on channel properties.…”

Section: Overview Of Cacna1c and Cacna1d...mentioning

confidence: 99%

L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development

2023

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Recent human genetic studies have linked a variety of genetic variants in the CACNA1C and CACNA1D genes to neuropsychiatric and neurodevelopmental disorders. This is not surprising given the work from multiple laboratories using cell and animal models that have established that Ca v 1.2 and Ca v 1.3 L-type calcium channels (LTCCs), encoded by CACNA1C and CACNA1D , respectively, play a key role in various neuronal processes that are essential for normal brain development, connectivity, and experience-dependent plasticity. Of the multiple genetic aberrations reported, genome-wide association studies (GWASs) have identified multiple single nucleotide polymorphisms (SNPs) in CACNA1C and CACNA1D that are present within introns, in accordance with the growing body of literature establishing that large numbers of SNPs associated with complex diseases, including neuropsychiatric disorders, are present within non-coding regions. How these intronic SNPs affect gene expression has remained a question. Here, we review recent studies that are beginning to shed light on how neuropsychiatric-linked non-coding genetic variants can impact gene expression via regulation at the genomic and chromatin levels. We additionally review recent studies that are uncovering how altered calcium signaling through LTCCs impact some of the neuronal developmental processes, such as neurogenesis, neuron migration, and neuron differentiation. Together, the described changes in genomic regulation and disruptions in neurodevelopment provide possible mechanisms by which genetic variants of LTCC genes contribute to neuropsychiatric and neurodevelopmental disorders.

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CACNA1D-Related Channelopathies: From Hypertension to Autism

Cited by 8 publications

References 146 publications

Unveiling the role of tRNA-derived small RNAs in MAPK signaling pathway: implications for cancer and beyond

Unveiling the role of tRNA-derived small RNAs in MAPK signaling pathway: implications for cancer and beyond

Pathophysiology of Cav1.3 L-type calcium channels in the heart

L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development

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