scholarly journals Compartmentalization of Photoreceptor Sensory Cilia

2021 ◽  
Vol 9 ◽  
Author(s):  
Cassandra L. Barnes ◽  
Himanshu Malhotra ◽  
Peter D. Calvert
Keyword(s):  
Plasma Membranes ◽  
Primary Cilia ◽  
Molecular Mechanisms ◽  
Sensory Cilia ◽  
Ciliary Protein ◽  
Olfactory Cells ◽  
Physiological Demands ◽  
Photoreceptor Neurons ◽  
Membrane Compartmentalization ◽  
Physical And Chemical

Functional compartmentalization of cells is a universal strategy for segregating processes that require specific components, undergo regulation by modulating concentrations of those components, or that would be detrimental to other processes. Primary cilia are hair-like organelles that project from the apical plasma membranes of epithelial cells where they serve as exclusive compartments for sensing physical and chemical signals in the environment. As such, molecules involved in signal transduction are enriched within cilia and regulating their ciliary concentrations allows adaptation to the environmental stimuli. The highly efficient organization of primary cilia has been co-opted by major sensory neurons, olfactory cells and the photoreceptor neurons that underlie vision. The mechanisms underlying compartmentalization of cilia are an area of intense current research. Recent findings have revealed similarities and differences in molecular mechanisms of ciliary protein enrichment and its regulation among primary cilia and sensory cilia. Here we discuss the physiological demands on photoreceptors that have driven their evolution into neurons that rely on a highly specialized cilium for signaling changes in light intensity. We explore what is known and what is not known about how that specialization appears to have driven unique mechanisms for photoreceptor protein and membrane compartmentalization.

scholarly journals Heavy Silicone Oil and Intraocular Inflammation

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Francesco Morescalchi ◽  
Ciro Costagliola ◽  
Sarah Duse ◽  
Elena Gambicorti ◽  
Barbara Parolini ◽  
...  
Keyword(s):  
Specific Gravity ◽  
Molecular Mechanisms ◽  
Silicone Oil ◽  
Surgical Techniques ◽  
Chemical Properties ◽  
Intraocular Inflammation ◽  
Retinal Breaks ◽  
Oxane Hd ◽  
Long Acting ◽  
Physical And Chemical

In the past two decades, many advances have been made in vitrectomy instrumentation, surgical techniques, and the use of different tamponade agents. These agents serve close retinal breaks, confine eventual retinal redetachment, and prevent proliferative vitreoretinopathy (PVR). Long-acting gases and silicone oil are effective internal tamponade agents; however, because their specific gravity is lower than that of the vitreous fluid, they may provide adequate support for the superior retina but lack efficacy for the inferior retina, especially when the fill is subtotal. Thus, a specific role may exist for an internal tamponade agent with a higher specific gravity, such as heavy silicone oils (HSOs), Densiron 68, Oxane HD, HWS 45-300, HWS 46-3000, and HeavySil. Some clinical evidence seems to presume that heavy tamponades are more prone to intraocular inflammation than standard silicone if they remain in the eye for several months. In this review, we discuss the fundamental clinical and biochemical/molecular mechanisms involved in the inflammatory response after the use of heavy tamponade: toxicity due to impurities or instability of the agent, direct toxicity and immunogenicity, oil emulsification, and mechanical injury due to gravity. The physical and chemical properties of various HSOs and their efficacy and safety profiles are also described.

scholarly journals CNPY4 inhibits the Hedgehog pathway by modulating membrane sterol lipids

2021 ◽  
Author(s):  
Megan Lo ◽  
Amnon Sharir ◽  
Michael D Paul ◽  
Hayarpi Torosyan ◽  
Christopher Agnew ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Primary Cilia ◽  
Molecular Mechanisms ◽  
Negative Regulator ◽  
Membrane Composition ◽  
Hh Signaling ◽  
Pathway Regulation ◽  
Patched 1 ◽  
Cancer Signal Transduction

The Hedgehog (HH) pathway is critical for development and adult tissue homeostasis. Aberrant HH signaling can cause congenital malformations, such as digit anomalies and holoprosencephaly, and other diseases, including cancer. Signal transduction is initiated by HH ligand binding to the Patched 1 (PTCH1) receptor on primary cilia, thereby releasing inhibition of Smoothened (SMO), a HH pathway activator. Although cholesterol and several oxysterol lipids, which are enriched in the ciliary membrane, play a crucial role in HH activation, the molecular mechanisms governing the regulation of these lipid molecules remain unresolved. Here, we identify Canopy 4 (CNPY4), a Saposin-like protein, as a regulator of the HH pathway that controls membrane sterol lipid levels. Cnpy4—/— embryos exhibit multiple defects consistent with HH signaling perturbations, most notably changes in digit number. Knockdown of Cnpy4 hyperactivates the HH pathway at the level of SMO in vitro, and elevates membrane levels of accessible sterol lipids such as cholesterol, an endogenous ligand involved in SMO activation. Thus, our data demonstrate that CNPY4 is a negative regulator that fine-tunes the initial steps of HH signal transduction, revealing a previously undescribed facet of HH pathway regulation that operates through control of membrane composition.

scholarly journals A Model for Primary Cilium Biogenesis by Polarized Epithelial Cells: Role of the Midbody Remnant and Associated Specialized Membranes

2021 ◽  
Vol 8 ◽  
Author(s):  
Leticia Labat-de-Hoz ◽  
Armando Rubio-Ramos ◽  
Javier Casares-Arias ◽  
Miguel Bernabé-Rubio ◽  
Isabel Correas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Control Cell ◽  
Future Research ◽  
Alternative Route ◽  
Ciliary Membrane ◽  
Cilium Formation ◽  
Membrane Compartmentalization

Primary cilia are solitary, microtubule-based protrusions surrounded by a ciliary membrane equipped with selected receptors that orchestrate important signaling pathways that control cell growth, differentiation, development and homeostasis. Depending on the cell type, primary cilium assembly takes place intracellularly or at the cell surface. The intracellular route has been the focus of research on primary cilium biogenesis, whereas the route that occurs at the cell surface, which we call the “alternative” route, has been much less thoroughly characterized. In this review, based on recent experimental evidence, we present a model of primary ciliogenesis by the alternative route in which the remnant of the midbody generated upon cytokinesis acquires compact membranes, that are involved in compartmentalization of biological membranes. The midbody remnant delivers part of those membranes to the centrosome in order to assemble the ciliary membrane, thereby licensing primary cilium formation. The midbody remnant's involvement in primary cilium formation, the regulation of its inheritance by the ESCRT machinery, and the assembly of the ciliary membrane from the membranes originally associated with the remnant are discussed in the context of the literature concerning the ciliary membrane, the emerging roles of the midbody remnant, the regulation of cytokinesis, and the role of membrane compartmentalization. We also present a model of cilium emergence during evolution, and summarize the directions for future research.

scholarly journals A hypothesis to reconcile the physical and chemical unfolding of proteins

2015 ◽  
Vol 112 (21) ◽  
pp. E2775-E2784 ◽  
Author(s):  
Guilherme A. P. de Oliveira ◽  
Jerson L. Silva
Keyword(s):  
Molecular Mechanisms ◽  
Chemical Shifts ◽  
Mechanistic Model ◽  
Solvent System ◽  
Threshold Concentration ◽  
Moniliophthora Perniciosa ◽  
X Ray ◽  
X Ray Scattering ◽  
Physical And Chemical ◽  
Ray Scattering

High pressure (HP) or urea is commonly used to disturb folding species. Pressure favors the reversible unfolding of proteins by causing changes in the volumetric properties of the protein–solvent system. However, no mechanistic model has fully elucidated the effects of urea on structure unfolding, even though protein–urea interactions are considered to be crucial. Here, we provide NMR spectroscopy and 3D reconstructions from X-ray scattering to develop the “push-and-pull” hypothesis, which helps to explain the initial mechanism of chemical unfolding in light of the physical events triggered by HP. In studying MpNep2 from Moniliophthora perniciosa, we tracked two cooperative units using HP-NMR as MpNep2 moved uphill in the energy landscape; this process contrasts with the overall structural unfolding that occurs upon reaching a threshold concentration of urea. At subdenaturing concentrations of urea, we were able to trap a state in which urea is preferentially bound to the protein (as determined by NMR intensities and chemical shifts); this state is still folded and not additionally exposed to solvent [fluorescence and small-angle X-ray scattering (SAXS)]. This state has a higher susceptibility to pressure denaturation (lower p1/2 and larger ΔVu); thus, urea and HP share concomitant effects of urea binding and pulling and water-inducing pushing, respectively. These observations explain the differences between the molecular mechanisms that control the physical and chemical unfolding of proteins, thus opening up new possibilities for the study of protein folding and providing an interpretation of the nature of cooperativity in the folding and unfolding processes.

scholarly journals Friend or Foe: Interbacterial Competition in the Nasal Cavity

2020 ◽  
Author(s):  
Britney L. Hardy ◽  
D. Scott Merrell
Keyword(s):  
Immune System ◽  
Nasal Cavity ◽  
Human Body ◽  
Molecular Mechanisms ◽  
Upper Respiratory Tract ◽  
Competition And Cooperation ◽  
Age Dependent ◽  
Upper Respiratory ◽  
Physical And Chemical ◽  
Nasal Microbiota

Like other microbes that live on or in the human body, the bacteria that inhabit the upper respiratory tract, in particular the nasal cavity, have evolved to survive in an environment that presents a number of physical and chemical challenges; these microbes are constantly bombarded with nutritional fluctuations, changes in humidity, the presence of inhaled particulate matter (odorants, allergens), and competition with other microbes. Indeed, only a specialized set of species are able to colonize this niche and successfully contend with the host's immune system and the constant threat from competitors. To this end, bacteria that live in the nasal cavity have evolved a variety of approaches to outcompete contenders for the limited nutrients and space; broadly speaking, these strategies may be considered a type of ‘bacterial warfare’. A greater molecular understanding of bacterial warfare has the potential to reveal new approaches or molecules that can be developed as novel therapeutics. As such, there are many studies within the last decade that have sought to understand the complex polymicrobial interactions that occur in various environments. Herein, we review what is currently known about the age-dependent structure and interbacterial relationships within the nasal microbiota and summarize the molecular mechanisms that are predicted to dictate bacterial warfare in this niche. Though the currently described interactions are complex, in reality we have likely only scratched the surface in terms of a true understanding of the types of interbacterial competition and cooperation that are thought to take place in and on the human body.

Activity and Phylogenetics of the Broadly Occurring Family of Microbial Nep1-Like Proteins

2019 ◽  
Vol 57 (1) ◽  
pp. 367-386 ◽  
Author(s):  
Michael F. Seidl ◽  
Guido Van den Ackerveken
Keyword(s):  
Arabidopsis Thaliana ◽  
Plant Species ◽  
Historical Perspective ◽  
Plasma Membranes ◽  
Molecular Mechanisms ◽  
Plant Immunity ◽  
Taxonomic Distribution ◽  
Outer Leaflet ◽  
Molecular Patterns ◽  
Shed Light

Necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLP) have an extremely broad taxonomic distribution; they occur in bacteria, fungi, and oomycetes. NLPs come in two forms, those that are cytotoxic to eudicot plants and those that are noncytotoxic. Cytotoxic NLPs bind to glycosyl inositol phosphoryl ceramide (GIPC) sphingolipids that are abundant in the outer leaflet of plant plasma membranes. Binding allows the NLP to become cytolytic in eudicots but not monocots. The function of noncytotoxic NLPs remains enigmatic, but the expansion of NLP genes in oomycete genomes suggests they are important. Several plant species have evolved the capacity to recognize NLPs as molecular patterns and trigger plant immunity, e.g., Arabidopsis thaliana detects nlp peptides via the receptor-like protein RLP23. In this review, we provide a historical perspective from discovery to understanding of molecular mechanisms and describe the latest developments in the NLP field to shed light on these fascinating microbial proteins.

scholarly journals Biology, Pathophysiological Role, and Clinical Implications of Exosomes: A Critical Appraisal

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 99 ◽  
Author(s):  
Arif Jan ◽  
Safikur Rahman ◽  
Shahanavaj Khan ◽  
Sheikh Tasduq ◽  
Inho Choi
Keyword(s):  
Plasma Membranes ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Target Cells ◽  
Host Immune System ◽  
Messenger Rnas ◽  
Extracellular Milieu ◽  
Tumor Microenvironments ◽  
Physiological Processes ◽  
Antigen Presenting

Exosomes are membrane-enclosed entities of endocytic origin, which are generated during the fusion of multivesicular bodies (MVBs) and plasma membranes. Exosomes are released into the extracellular milieu or body fluids; this process was reported for mesenchymal, epithelial, endothelial, and different immune cells (B-cells and dendritic cells), and was reported to be correlated with normal physiological processes. The compositions and abundances of exosomes depend on their tissue origins and cell types. Exosomes range in size between 30 and 100 nm, and shuttle nucleic acids (DNA, messenger RNAs (mRNAs), microRNAs), proteins, and lipids between donor and target cells. Pathogenic microorganisms also secrete exosomes that modulate the host immune system and influence the fate of infections. Such immune-modulatory effect of exosomes can serve as a diagnostic biomarker of disease. On the other hand, the antigen-presenting and immune-stimulatory properties of exosomes enable them to trigger anti-tumor responses, and exosome release from cancerous cells suggests they contribute to the recruitment and reconstitution of components of tumor microenvironments. Furthermore, their modulation of physiological and pathological processes suggests they contribute to the developmental program, infections, and human diseases. Despite significant advances, our understanding of exosomes is far from complete, particularly regarding our understanding of the molecular mechanisms that subserve exosome formation, cargo packaging, and exosome release in different cellular backgrounds. The present study presents diverse biological aspects of exosomes, and highlights their diagnostic and therapeutic potentials.

scholarly journals Induction of Ran GTP drives ciliogenesis

2011 ◽  
Vol 22 (23) ◽  
pp. 4539-4548 ◽  
Author(s):  
Shuling Fan ◽  
Eileen L. Whiteman ◽  
Toby W. Hurd ◽  
Jeremy C. McIntyre ◽  
John F. Dishinger ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Protein Transport ◽  
Nucleocytoplasmic Transport ◽  
Small Gtpase ◽  
Basal Bodies ◽  
Ciliary Protein ◽  
Cilia Formation ◽  
Ran Gtp ◽  
New Evidence ◽  
Gtpase Ran

The small GTPase Ran and the importin proteins regulate nucleocytoplasmic transport. New evidence suggests that Ran GTP and the importins are also involved in conveying proteins into cilia. In this study, we find that Ran GTP accumulation at the basal bodies is coordinated with the initiation of ciliogenesis. The Ran-binding protein 1 (RanBP1), which indirectly accelerates Ran GTP → Ran GDP hydrolysis and promotes the dissociation of the Ran/importin complex, also localizes to basal bodies and cilia. To confirm the crucial link between Ran GTP and ciliogenesis, we manipulated the levels of RanBP1 and determined the effects on Ran GTP and primary cilia formation. We discovered that RanBP1 knockdown results in an increased concentration of Ran GTP at basal bodies, leading to ciliogenesis. In contrast, overexpression of RanBP1 antagonizes primary cilia formation. Furthermore, we demonstrate that RanBP1 knockdown disrupts the proper localization of KIF17, a kinesin-2 motor, at the distal tips of primary cilia in Madin–Darby canine kidney cells. Our studies illuminate a new function for Ran GTP in stimulating cilia formation and reinforce the notion that Ran GTP and the importins play key roles in ciliogenesis and ciliary protein transport.

Expression of membrane-associated carbonic anhydrase isoforms IV, IX, XII, and XIV in the rabbit: induction of CA IV and IX during maturation

2005 ◽  
Vol 288 (5) ◽  
pp. R1256-R1263 ◽  
Author(s):  
Jeffrey M. Purkerson ◽  
George J. Schwartz
Keyword(s):  
Skeletal Muscle ◽  
Carbonic Anhydrase ◽  
Gall Bladder ◽  
Plasma Membranes ◽  
Rabbit Kidney ◽  
Α Subunit ◽  
Anion Transporters ◽  
Ca Ix ◽  
Membrane Bound ◽  
Physiological Demands

Several carbonic anhydrase (CA) isoforms are associated with plasma membranes. It is probable that these enzymes interact with anion transporters to facilitate the movement of HCO3− into or out of the cell. A better knowledge of CA isoform expression in a given tissue would facilitate a systematic examination of any associations with such transporters. We examined the expression of CAs IV, IX, XII, and XIV mRNAs in rabbit tissues, including kidney, heart, lung, skeletal muscle, liver, pancreas, gall bladder, stomach, small intestine, colon, and spleen, using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). CA IV mRNA was mainly in kidney, heart, lung, colon, and gall bladder. CA IX mRNA was restricted to stomach, gall bladder, duodenum, and early jejunum. CA XII mRNA was found in kidney and colon. CA XIV mRNA was localized to heart, lung, skeletal muscle, and liver. The data indicate that there are different patterns of CA expression in various tissues: CA IX was expressed in the proximal gastrointestinal tract, whereas CA XII and CA IV were more distal. CA IV and CA XII are important kidney isoforms. CA XIV was abundant in metabolically active tissues such as liver, heart, lung, and skeletal muscle. Some significant species differences were noted in the expression of some of these isoforms; for example, CA XIV is not expressed in rabbit kidney, despite being abundant in mouse kidney. Maturational studies showed that the expression of CA IX mRNA and protein increased markedly with weaning (∼3–4 postnatal wk) and was well correlated with the maturational expression of the α-subunit of the gastric H+,K+-ATPase, suggesting that function of CA IX and the gastric H+ pump might be linked in the digestion of adult foodstuffs. The unique pattern of membrane-bound CA isoforms suggests different functional associations with transporters, depending on the physiological demands on the tissue.

scholarly journals Junctional adhesion molecule (JAM) binds to PAR-3

2001 ◽  
Vol 154 (3) ◽  
pp. 491-498 ◽  
Author(s):  
Masahiko Itoh ◽  
Hiroyuki Sasaki ◽  
Mikio Furuse ◽  
Harunobu Ozaki ◽  
Toru Kita ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Plasma Membranes ◽  
Molecular Mechanisms ◽  
Spatial Relationship ◽  
Immunoglobulin Superfamily ◽  
Binding Assays ◽  
Adhesion Sites ◽  
Vitro Binding ◽  
Self Association

At tight junctions (TJs), claudins with four transmembrane domains are incorporated into TJ strands. Junctional adhesion molecule (JAM), which belongs to the immunoglobulin superfamily, is also localized at TJs, but it remains unclear how JAM is integrated into TJs. Immunoreplica electron microscopy revealed that JAM showed an intimate spatial relationship with TJ strands in epithelial cells. In L fibroblasts expressing exogenous JAM, JAM was concentrated at cell–cell adhesion sites, where there were no strand-like structures, but rather characteristic membrane domains free of intramembranous particles were detected. These domains were specifically labeled with anti-JAM polyclonal antibody, suggesting that JAM forms planar aggregates through their lateral self-association. Immunofluorescence microscopy and in vitro binding assays revealed that ZO-1 directly binds to the COOH termini of claudins and JAM at its PDZ1 and PDZ3 domains, respectively. Furthermore, another PDZ-containing polarity-related protein, PAR-3, was directly bound to the COOH terminus of JAM, but not to that of claudins. These findings led to a molecular architectural model for TJs: small aggregates of JAM are tethered to claudin-based strands through ZO-1, and these JAM aggregates recruit PAR-3 to TJs. We also discuss the importance of this model from the perspective of the general molecular mechanisms behind the recruitment of PAR proteins to plasma membranes.

Sign in / Sign up

Export Citation Format

Share Document