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Progress in Molecular and Subcellular Biology

Alicia Daeden, Marcos Gonzalez-Gaitan
Endocytosis is key in a number of cell events. In particular, its role during cell division has been a challenging question: while early studies examined whether endocytosis occurs during cell division, recent works show that, during division, cells do perform endocytosis actively. More importantly, during asymmetric cell division, endocytic pathways also control Notch signaling: endocytic vesicles regulate the presence, at the plasma membrane, of receptors and ligands at different levels between the two-daughter cells...
2018: Progress in Molecular and Subcellular Biology
Silvia Sposini, Aylin C Hanyaloglu
The G protein-coupled receptor (GPCR) superfamily activates complex signal pathways, yet untangling these signaling systems to understand how specificity in receptor signaling pathways is achieved, has been a challenging question. The roles of membrane trafficking in GPCR signal regulation has undergone a recent paradigm shift, from a mechanism that programs the plasma membrane G protein signaling profile to providing distinct signaling platforms critical for specifying receptor function in vivo. In this chapter, we discuss this evolution of our understanding in the endocytic trafficking systems employed by GPCRs, and how such systems play a deeply integrated role with signaling...
2018: Progress in Molecular and Subcellular Biology
Giusi Caldieri, Maria Grazia Malabarba, Pier Paolo Di Fiore, Sara Sigismund
Signaling from the epidermal growth factor receptor (EGFR) elicits multiple biological responses, including cell proliferation, migration, and survival. Receptor endocytosis and trafficking are critical physiological processes that control the strength, duration, diversification, and spatial restriction of EGFR signaling through multiple mechanisms, which we review in this chapter. These mechanisms include: (i) regulation of receptor density and activation at the cell surface; (ii) concentration of receptors into distinct nascent endocytic structures; (iii) commitment of the receptor to different endocytic routes; (iv) endosomal sorting and postendocytic trafficking of the receptor through distinct pathways, and (v) recycling to restricted regions of the cell surface...
2018: Progress in Molecular and Subcellular Biology
Olivia Muriel, Miguel Sánchez-Álvarez, Raffaele Strippoli, Miguel Angel Del Pozo
Caveolae are 60-80 nm invaginated plasma membrane (PM) nanodomains, with a specific lipid and protein composition, which assist and regulate multiple processes in the plasma membrane-ranging from the organization of signalling complexes to the mechanical adaptation to changes in PM tension. However, since their initial descriptions, these structures have additionally been found tightly linked to internalization processes, mechanoadaptation, to the regulation of signalling events and of endosomal trafficking...
2018: Progress in Molecular and Subcellular Biology
Rachel Moore, Marta Giralt Pujol, Zhou Zhu, Elizabeth Smythe
Growth factor receptors play a variety of roles during embryonic development and in adult homeostasis. These receptors are activated repeatedly in different cellular contexts and with different cellular outcomes. This begs the question as to how cells in a particular developmental, spatial and temporal context, or in adult tissue, interpret signalling by growth factor receptors in order to deliver qualitatively different signalling outputs. One mechanism by which this could occur is via endocytic regulation...
2018: Progress in Molecular and Subcellular Biology
Geoffrey G Hesketh, Lena Wartosch, Luther J Davis, Nicholas A Bright, J Paul Luzio
In addition to being the terminal degradative compartment of the cell's endocytic and autophagic pathways, the lysosome is a multifunctional signalling hub integrating the cell's response to nutrient status and growth factor/hormone signalling. The cytosolic surface of the limiting membrane of the lysosome is the site of activation of the multiprotein complex mammalian target of rapamycin complex 1 (mTORC1), which phosphorylates numerous cell growth-related substrates, including transcription factor EB (TFEB)...
2018: Progress in Molecular and Subcellular Biology
Matthew N J Seaman
The retromer complex is a key element of the endosomal protein sorting machinery being involved in trafficking of proteins from endosomes to the Golgi and also endosomes to the cell surface. There is now accumulating evidence that retromer also has a prominent role in regulating the activity of many diverse signaling proteins that traffic through endosomes and this activity has profound implications for the functioning of many different cell and tissue types from neuronal cells to cells of the immune system to specialized polarized epithelial cells of the retina...
2018: Progress in Molecular and Subcellular Biology
Simona M Migliano, David Teis
The ubiquitin-dependent degradation of membrane proteins via the multivesicular body (MVB) pathway requires the Endosomal Sorting Complexes Required for Transport (ESCRT). This molecular machinery is composed of five distinct multi-subunit complexes. On the surface of endosomes, ESCRT-0, -I and -II bind to ubiquitinated membrane proteins, while ESCRT-III and Vps4 bud intraluminal vesicles (ILVs) into the lumen of the endosomes. By working together, ESCRTs package membrane proteins into ILVs and thereby generate MVBs...
2018: Progress in Molecular and Subcellular Biology
Francesc Tebar, Carlos Enrich, Carles Rentero, Thomas Grewal
The endocytic compartment is not only the functional continuity of the plasma membrane but consists of a diverse collection of intracellular heterogeneous complex structures that transport, amplify, sustain, and/or sort signaling molecules. Over the years, it has become evident that early, late, and recycling endosomes represent an interconnected vesicular-tubular network able to form signaling platforms that dynamically and efficiently translate extracellular signals into biological outcome. Cell activation, differentiation, migration, death, and survival are some of the endpoints of endosomal signaling...
2018: Progress in Molecular and Subcellular Biology
Noga Budick-Harmelin, Marta Miaczynska
Maintenance of physiologic cellular functions and homeostasis requires highly coordinated interactions between different cellular compartments. In this regard, the endocytic system, which plays a key role in cargo internalization and trafficking within the cell, participates in upkeep of intracellular dynamics, while communicating with multiple organelles. This chapter will discuss the function of endosomes from a standpoint of cellular integration. We will present examples of different types of interactions between endosomes and other cellular compartments, such as the endoplasmic reticulum (ER), mitochondria, the plasma membrane (PM), and the nuclear envelope...
2018: Progress in Molecular and Subcellular Biology
Maria Podinovskaia, Anne Spang
Endocytosis is a means for the cell to sample its environment for nutrients and regulate plasma membrane (PM) composition and area. Whereas the majority of internalized cargo is recycled back to the cell surface, select material is sent to the lysosome for degradation. Endosomes further play major roles in central cell activities as diverse as establishment of cell polarity and signaling, lysosomal storage and immunity. The complexity of endosomal functions is reflected by the extensive changes to endosome properties as they mature...
2018: Progress in Molecular and Subcellular Biology
Thian Thian Beh, Paul Kalitsis
The accurate segregation of chromosomes to daughter cells is essential for healthy development to occur. Imbalances in chromosome number have long been associated with cancers amongst other medical disorders. Little is known whether abnormal chromosome numbers are an early contributor to the cancer progression pathway. Centromere DNA and protein defects are known to impact on the fidelity of chromosome segregation in cell and model systems. In this chapter we discuss recent developments in understanding the contribution of centromere abnormalities at the protein and DNA level and their role in cancer in human and mouse systems...
2017: Progress in Molecular and Subcellular Biology
Kerry Bloom, Vincenzo Costanzo
The centromere is the genetic locus that specifies the site of kinetochore assembly, where the chromosome will attach to the kinetochore microtubule. The pericentromere is the physical region responsible for the geometry of bi-oriented sister kinetochores in metaphase. In budding yeast the 125 bp point centromere is sufficient to specify kinetochore assembly. The flanking region is enriched (3X) in cohesin and condensin relative to the remaining chromosome arms. The enrichment spans about 30-50 kb around each centromere...
2017: Progress in Molecular and Subcellular Biology
Mihailo Mirkovic, Raquel A Oliveira
Sister chromatid cohesion, mediated by the cohesin complex, is a prerequisite for faithful chromosome segregation during mitosis. Premature release of sister chromatid cohesion leads to random segregation of the genetic material and consequent aneuploidy. Multiple regulatory mechanisms ensure proper timing for cohesion establishment, concomitant with DNA replication, and cohesion release during the subsequent mitosis. Here we summarize the most important phases of the cohesin cycle and the coordination of cohesion release with the progression through mitosis...
2017: Progress in Molecular and Subcellular Biology
Giulia Vallardi, Marilia Henriques Cordeiro, Adrian Thomas Saurin
The KMN network (for KNL1, MIS12 and NDC80 complexes) is a hub for signalling at the outer kinetochore. It integrates the activities of two kinases (MPS1 and Aurora B) and two phosphatases (PP1 and PP2A-B56) to regulate kinetochore-microtubule attachments and the spindle assembly checkpoint (SAC). We will first discuss each of these enzymes separately, to describe how they are regulated at kinetochores and why this is important for their primary function in controlling either microtubule attachments or the SAC...
2017: Progress in Molecular and Subcellular Biology
Kevin D Corbett
In eukaryotic cell division, the Spindle Assembly Checkpoint (SAC) plays a key regulatory role by monitoring the status of chromosome-microtubule attachments and allowing chromosome segregation only after all chromosomes are properly attached to spindle microtubules. While the identities of SAC components have been known, in some cases, for over two decades, the molecular mechanisms of the SAC have remained mostly mysterious until very recently. In the past few years, advances in biochemical reconstitution, structural biology, and bioinformatics have fueled an explosion in the molecular understanding of the SAC...
2017: Progress in Molecular and Subcellular Biology
Ekaterina L Grishchuk
The main physiological function of mitotic kinetochores is to provide durable attachment to spindle microtubules, which segregate chromosomes in order to partition them equally between the two daughter cells. Numerous kinetochore components that can bind directly to microtubules have been identified, including ATP-dependent motors and various microtubule-associated proteins with no motor activity. A major challenge facing the field is to explain chromosome motions based on the biochemical and structural properties of these individual kinetochore components and their assemblies...
2017: Progress in Molecular and Subcellular Biology
Lukáš Chmátal, Richard M Schultz, Ben E Black, Michael A Lampson
Mendel's First Law of Genetics states that a pair of alleles segregates randomly during meiosis so that one copy of each is represented equally in gametes. Whereas male meiosis produces four equal sperm, in female meiosis only one cell, the egg, survives, and the others degenerate. Meiotic drive is a process in which a selfish DNA element exploits female meiotic asymmetry and segregates preferentially to the egg in violation of Mendel's First Law, thereby increasing its transmission to the offspring and frequency in a population...
2017: Progress in Molecular and Subcellular Biology
Elaine M Dunleavy, Caitríona M Collins
In sexually reproducing organisms the germ line is the cellular lineage that gives rise to gametes. All germ cells originate from germline stem cells that divide asymmetrically to generate gonial pre-cursors, which are amplified in number by mitotic divisions, undergo meiosis and eventually differentiate into mature gametes (haploid eggs and sperm). Information transmitted with gametes is inherited by offspring, and potentially by subsequent generations, instructing in organismal development and beyond. Meiosis comprises one round of DNA replication, followed by two rounds of chromosome segregation; homologous chromosomes segregate in the first division (meiosis I) and sister chromatids segregate in the second division (meiosis II)...
2017: Progress in Molecular and Subcellular Biology
Elena Giulotto, Elena Raimondi, Kevin F Sullivan
Centromeres are highly distinctive genetic loci whose function is specified largely by epigenetic mechanisms. Understanding the role of DNA sequences in centromere function has been a daunting task due to the highly repetitive nature of centromeres in animal chromosomes. The discovery of a centromere devoid of satellite DNA in the domestic horse consolidated observations on the epigenetic nature of centromere identity, showing that entirely natural chromosomes could function without satellite DNA cues. Horses belong to the genus Equus which exhibits a very high degree of evolutionary plasticity in centromere position and DNA sequence composition...
2017: Progress in Molecular and Subcellular Biology
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