Organization and functions of glycolipid-enriched microdomains in phagocytes

Ekyalongo, Roudy Chiminch; Nakayama, Hitoshi; Kina, Katsunari; Kaga, Naoko; Iwabuchi, Kazuhisa

doi:10.1016/j.bbalip.2014.06.009

Cited by 30 publications

(24 citation statements)

References 67 publications

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“…Finally, we note that many toxins and viruses utilize a multivalent glycolipid binding strategy to gain access to host cells (23,24). Further, clustering of glycolipids has been hypothesized to play a role in many cellular functions (25)(26)(27)(28). Our results validate the underlying assumption in these biological scenarios that clustering of glycolipids enables raft partitioning and stabilization.…”

supporting

confidence: 76%

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

Raghunathan

Wong

Chinnapen

et al. 2017

Biophysical Journal

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Current models of lipid rafts propose that lipid domains exist as nanoscale compositional fluctuations and these fluctuations can potentially be stabilized into larger domains, consequently better compartmentalizing cellular functions. However, the mechanisms governing stabilized raft assembly and function remain unclear. Here, we test the role of glycolipid crosslinking as a raft targeting and ordering mechanism using the well-studied raft marker cholera toxin B pentamer (CTxB) that binds up to five GM1 glycosphingolipids to enter host cells. We show that when applied to cell-derived giant plasma membrane vesicles, a variant of CTxB containing only a single functional GM1 binding site exhibits significantly reduced partitioning to the ordered phase compared to wild-type CTxB with five binding sites. Moreover, monovalent CTxB does not stabilize membrane domains, unlike wild-type CTxB. These results support the long-held hypothesis that CTxB stabilizes raft domains via a lipid crosslinking mechanism and establish a role for crosslinking in the partitioning of CTxB to ordered domains.

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supporting

confidence: 76%

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

Raghunathan

Wong

Chinnapen

et al. 2017

Biophysical Journal

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“…Caveolae are small 50–100 nm invaginations of the plasma membrane where the protein caveolin associates with membrane enriched in cholesterol and sphingolipids [15]. However, sphingolipid- and cholesterol-dependent microdomains with a diameter less than 20 nm and an average lifespan of 10–20 ms have been identified in living cells [16,17]. …”

Section: Introductionmentioning

confidence: 99%

Sphingolipids: membrane microdomains in brain development, function and neurological diseases

Olsen¹,

Færgeman²

2017

Open Biol.

253

199

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Sphingolipids are highly enriched in the nervous system where they are pivotal constituents of the plasma membranes and are important for proper brain development and functions. Sphingolipids are not merely structural elements, but are also recognized as regulators of cellular events by their ability to form microdomains in the plasma membrane. The significance of such compartmentalization spans broadly from being involved in differentiation of neurons and synaptic transmission to neuronal–glial interactions and myelin stability. Thus, perturbations of the sphingolipid metabolism can lead to rearrangements in the plasma membrane, which has been linked to the development of various neurological diseases. Studying microdomains and their functions has for a long time been synonymous with studying the role of cholesterol. However, it is becoming increasingly clear that microdomains are very heterogeneous, which among others can be ascribed to the vast number of sphingolipids. In this review, we discuss the importance of microdomains with emphasis on sphingolipids in brain development and function as well as how disruption of the sphingolipid metabolism (and hence microdomains) contributes to the pathogenesis of several neurological diseases.

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“…Finally, CD44 associates with EMT-related transcription factors, e.g., the Wnt signaling pathway via CD44-associated LRP6 (LDL receptor related protein6) (Xu et al, 2015). Of central importance for the engagement of CD44 as a CIC marker are the associations with non-RTK (Cooper and Qian, 2008; Nastase et al, 2017), which can proceed via activated RTK, GPCR, cytoskeletal linker proteins, or directly via GEM-recruited CD44v (Ingley, 2008; Ekyalongo et al, 2015; Korcsmaros et al, 2017). …”

Section: Introductionmentioning

confidence: 99%

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

Wang

Zhao

Hackert

et al. 2018

Front. Cell Dev. Biol.

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Metastasis is the leading cause of cancer death, tumor progression proceeding through emigration from the primary tumor, gaining access to the circulation, leaving the circulation, settling in distant organs and growing in the foreign environment. The capacity of a tumor to metastasize relies on a small subpopulation of cells in the primary tumor, so called cancer-initiating cells (CIC). CIC are characterized by sets of markers, mostly membrane anchored adhesion molecules, CD44v6 being the most frequently recovered marker. Knockdown and knockout models accompanied by loss of tumor progression despite unaltered primary tumor growth unraveled that these markers are indispensable for CIC. The unexpected contribution of marker molecules to CIC-related activities prompted research on underlying molecular mechanisms. This review outlines the contribution of CD44, particularly CD44v6 to CIC activities. A first focus is given to the impact of CD44/CD44v6 to inherent CIC features, including the crosstalk with the niche, apoptosis-resistance, and epithelial mesenchymal transition. Following the steps of the metastatic cascade, we report on supporting activities of CD44/CD44v6 in migration and invasion. These CD44/CD44v6 activities rely on the association with membrane-integrated and cytosolic signaling molecules and proteases and transcriptional regulation. They are not restricted to, but most pronounced in CIC and are tightly regulated by feedback loops. Finally, we discuss on the engagement of CD44/CD44v6 in exosome biogenesis, loading and delivery. exosomes being the main acteurs in the long-distance crosstalk of CIC with the host. In brief, by supporting the communication with the niche and promoting apoptosis resistance CD44/CD44v6 plays an important role in CIC maintenance. The multifaceted interplay between CD44/CD44v6, signal transducing molecules and proteases facilitates the metastasizing tumor cell journey through the body. By its engagement in exosome biogenesis CD44/CD44v6 contributes to disseminated tumor cell settlement and growth in distant organs. Thus, CD44/CD44v6 likely is the most central CIC biomarker.

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Organization and functions of glycolipid-enriched microdomains in phagocytes

Cited by 30 publications

References 67 publications

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

Glycolipid Crosslinking is Required for Cholera Toxin to Partition into and Stabilize Ordered Domains

Sphingolipids: membrane microdomains in brain development, function and neurological diseases

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

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