1,720,984 research outputs found
Regulation and function of PI4P at the Golgi complex
No full textFifty years after Bob Michell's visionary prediction, phosphatidylinositol 4-phosphate (PI4P) has emerged as a central regulator of Golgi function, influencing membrane trafficking, lipid metabolism, and signaling. PI4P homeostasis is tightly controlled by phosphatidylinositol 4-kinases (PI4Ks), phosphatidylinositol transfer proteins (PITPs), and the phosphatase SAC1, ensuring precise regulation across Golgi subdomains. Beyond its classical role in vesicular transport, PI4P orchestrates lipid exchange at membrane contact sites, enabling dynamic Golgi maturation and functional specialization. The interplay between PI4P, lipid transfer proteins, and Golgi adaptors underlies cargo sorting, glycosylation, and organelle architecture. Emerging evidence also highlights PI4P's role in oncogenesis and cellular signaling, positioning the Golgi as a critical hub beyond secretion. Yet, key questions remain regarding PI4P compartmentalization and its broader physiological impact. This review revisits PI4P's essential functions, integrating historical insights with recent discoveries to illuminate its pivotal role in Golgi biology and beyond
Cellular assays for drug discovery in genetic disorders of intracellular trafficking
No full textIntracellular membrane trafficking is essential for organelle biogenesis, structure, and function; the exchange of material between organelles; and communication between the cell and its external environment. Genetic disorders affecting intracellular trafficking can lead to a variety of human diseases, but specific therapies for these diseases are notably lacking. In this article, we focus on how current knowledge about genetic disorders that affect intracellular trafficking can be used to develop strategies for cell-based assays in order to identify drugs using high-content screening approaches
ER-Golgi membrane contact sites
No full textMembrane contact sites (MCSs) are sites where the membranes of two different organelles come into close apposition (10-30 nm). Different classes of proteins populate MCSs including factors that act as tethers between the two membranes, proteins that use the MCSs for their function (mainly lipid or ion exchange), and regulatory proteins and enzymes that can act in trans across the MCSs. The ER-Golgi MCSs were visualized by electron microscopists early in the sixties but have remained elusive for decades due to a lack of suitable methodological approaches. Here we report recent progress in the study of this class of MCSs that has led to the identification of their main morphological features and of some of their components and roles. Among these, lipid transfer proteins and lipid exchange have been the most studied and understood so far. However, many unknowns remain regarding their regulation and their role in controlling key TGN functions such as sorting and trafficking as well as their relevance in physiological and pathological conditions
Exiting the ER: What we know and what we don't
No full textThe vast majority of proteins that are transported to different cellular compartments and secreted from the cell require coat protein complex II (COPII) for export from the endoplasmic reticulum (ER). Many of the molecular mechanisms underlying COPII assembly are understood in great detail, but it is becoming increasingly evident that this basic machinery is insufficient to account for diverse aspects of protein export from the ER that are observed in vivo. Here we review recent data that have furthered our mechanistic understanding of COPII assembly and, in particular, how genetic diseases associated with the early secretory pathway have added fundamental insights into the regulation of ER-derived carrier formation. We also highlight some unresolved issues that future work should address to better understand the physiology of COPII-mediated transport
ER exit sites take the strain
No full textCells are able to adapt their growth to external mechanical strain. A recent study by Phuyal et al (2022) has shown that these responses depend on the heterodimerization of two small GTPases
TRAPPing Rab18 in lipid droplets
No full textA number of membrane trafficking components are associated with lipid droplets (LDs) and/or are involved in their biogenesis. In this issue of The EMBO Journal, Li et al (2016) show that the mammalian TRAPPII (TRAnsport Protein Particle) complex acts as an LD-associated GEF for Rab18, thereby regulating LD homeostasis. © 2017 EMBO
The Golgi apparatus: An organelle with multiple complex functions
No full textRemarkable advances have been made during the last few decades in defining the organizational principles of the secretory pathway. The Golgi complex in particular has attracted special attention due to its central position in the pathway, as well as for its fascinating and complex structure. Analytical studies of this organelle have produced significant advances in our understanding of its function, although some aspects still seem to elude our comprehension. In more recent years a level of complexity surrounding this organelle has emerged with the discovery that the Golgi complex is involved in cellular processes other than the 'classical' trafficking and biosynthetic pathways. The resulting picture is that the Golgi complex can be considered as a cellular headquarters where cargo sorting/processing, basic metabolism, signalling and cell-fate decisional processes converge
Ultrasonographic findings of fluid accumulation and hyperechogenic spots suggestive of surgical site infection following laparotomy for colic in horses
No full textBackground: The aim of this study was to compare ultrasonographic findings of the ventral midline incision after exploratory laparotomy for colic in horses with and without surgical site infection (SSI). Methods: Ultrasonographic examination of the surgical wound was performed on postoperative day 5 (D5) and day 10 (D10) to assess the presence of fluid accumulation, suture sinus formation, hyperechogenic spots and fistulous path. Clinical evaluation of the wound was used to classify horses with and without SSI. The accuracy, sensitivity, specificity and positive and negative predictive values of the ultrasonographic findings were then calculated. Multivariable logistic regression analyses were performed with SSI as a dependent variable and age, sex, breed and ultrasonographic findings as independent variables after univariate and collinearity analyses. Results: Twenty-nine of the 84 horses examined had an SSI. Detection of fluid accumulation and hyperechogenic spots increased the odds for SSI at D5 (odds ratio [OR]: 4.99, 95% confidence interval [CI]: 1.53-16.33, p = 0.008; OR: 10.78, 95% CI: 1.75-26.59, p = 0.01, respectively) and D10 (OR: 11.51, 95% CI: 2.39-55.47, p = 0.002; OR: 12.34, 95% CI: 3.45-44.15, p < 0.001, respectively). Limitation: Ultrasonographic images were taken only on the longitudinal section. Conclusion: Ultrasonographic examination is helpful in evaluating the surgical incision after laparotomy, with the detection of fluid accumulation and hyperechogenic spots surrounding the sutures being strongly related to SSI
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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