Abstract: In contrast to other Classical Transient Receptor Potential TRPC channels the function of TRPC1 as an ion channel is a matter of debate, because it is often difficult to obtain substantial functional signals over background in response to over-expression of TRPC1 alone. Along these lines, heterologously expressed TRPC1 is poorly translocated to the plasma membrane as a homotetramer and may not function on its own physiologically, but may rather be an important linker and regulator protein in heteromeric TRPC channel tetramers. However, due to the lack of specific TRPC1 antibodies able to detect native TRPC1 channels in primary cells, identification of functional TRPC1 containing heteromeric TRPC channel complexes in the plasma membrane is still challenging. Moreover, an extended TRPC1 cDNA, which was recently discovered, may seriously question results obtained in heterologous expression systems transfected with shortened cDNA versions. Therefore, this review will focus on the current status of research on TRPC1 function obtained in primary cells and a TRPC1-deficient mouse model.
Abstract: Transient Receptor Potential Vanilloid 1 (TRPV1) subunits form a polymodal cation channel responsive to capsaicin, heat, acidity and endogenous metabolites of polyunsaturated fatty acids. While originally reported to serve as a pain and heat detector in the peripheral nervous system, TRPV1 has been implicated in the modulation of blood flow and osmoregulation but also neurotransmission, postsynaptic neuronal excitability and synaptic plasticity within the central nervous system. In addition to its central role in nociception, evidence is accumulating that TRPV1 contributes to stimulus transduction and/or processing in other sensory modalities, including thermosensation, mechanotransduction and vision. For example, TRPV1, in conjunction with intrinsic cannabinoid signaling, might contribute to retinal ganglion cell (RGC) axonal transport and excitability, cytokine release from microglial cells and regulation of retinal vasculature. While excessive TRPV1 activity was proposed to induce RGC excitotoxicity, physiological TRPV1 activity might serve a neuroprotective function within the complex context of retinal endocannabinoid signaling. In this review we evaluate the current evidence for localization and function of TRPV1 channels within the mammalian retina and explore the potential interaction of this intriguing nociceptor with endogenous agonists and modulators.
Abstract: Cardiac Ca2+ cycling and signaling are closely associated with cardiac function. Changes in cellular Ca2+ homeostasis may lead to aberrant cardiac rhythm and may play a critical role in the pathogenesis of cardiac diseases, due to their exacerbation of heart failure. MicroRNAs (miRNAs) play a key role in the regulation of gene expression at the post-transcriptional level and participate in regulating diverse biological processes. The emerging evidence indicates that the expression profiles of miRNAs vary among human diseases, including cardiovascular diseases. Cardiac Ca2+-handling and signaling proteins are also regulated by miRNAs. Given the relationship between cardiac Ca2+ homeostasis and signaling and miRNA, Ca2+-related miRNAs may serve as therapeutic targets during the treatment of heart failure. In this review, we summarize the knowledge currently available regarding the role of Ca2+ in cardiac function, as well as changes in Ca2+ cycling and homeostasis and the handling of these processes by miRNAs during cardiac ischemia-reperfusion injury.
Abstract: It has been recognized for decades that proteins, which are encoded by our genome and produced via transcription and translation steps, are building blocks that play vital roles in almost all biological processes. Mutations identified in many protein-coding genes are linked to various human diseases. However, this “protein-centered” dogma has been challenged in recent years with the discovery that the majority of our genome is “non-coding” yet transcribed. Non-coding RNA has become the focus of “next generation” biology. Here, we review the emerging field of non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and their role in cardiovascular function and disease.
Abstract: The 3-dimensional spatial organization of eukaryotic genomes is important for regulation of gene expression as well as DNA damage repair. It has been proposed that one basic biophysical property of all nuclei is that interphase chromatin must be kept in a condensed prestressed state in order to prevent entropic pressure of the DNA polymer from expanding and disrupting the nuclear envelope. Although many factors can contribute to specific organizational states to compact chromatin, the mechanisms through which such interphase chromatin compaction is maintained are not clearly understood. Condensin proteins are known to exert compaction forces on chromosomes in anticipation of mitosis, but it is not known whether condensins also function to maintain interphase prestressed chromatin states. Here we show that RNAi depletion of the N-CAP-H2, N-CAP-D3 and SMC2 subunits of human condensin II leads to dramatic disruption of nuclear architecture and nuclear size. This is consistent with the idea that condensin mediated chromatin compaction contributes significantly to the prestressed condensed state of the interphase nucleus, and when such compaction forces are disrupted nuclear size and shape change due to chromatin expansion.
Abstract: Protein ubiquitination plays indispensable roles in the regulation of cell homeostasis and pathogenesis of neoplastic, infectious, and neurodegenerative diseases. Given the importance of this modification, it is to be expected that several pathogenic bacteria have developed the ability to utilize the host ubiquitin system for their own benefit. Modulation of the host ubiquitin system by bacterial effector proteins inhibits innate immune responses and hijacks central signaling pathways. Bacterial effectors mimic enzymes of the host ubiquitin system, but may or may not be structurally similar to the mammalian enzymes. Other effectors bind and modify components of the host ubiquitin system, and some are themselves subject to ubiquitination. This review will describe recent findings, based on structural analyses, regarding how pathogens use post-translational modifications of proteins to establish an infection.