Lipid raft integrity is required for human leukemia Jurkat T-cell migratory activity

Bobkov, Danila; Yudintceva, Natalia; Lomert, Ekaterina; Shatrova, A. N.; Kever, L. V.; Semenova, S. B.

doi:10.1016/j.bbalip.2021.158917

Cited by 11 publications

(18 citation statements)

References 51 publications

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“…Lymphocytespecific protein tyrosine kinase (Lck) is a member of the Src family of tyrosine kinases (SFKs); it phosphorylates tyrosine residues of certain proteins involved in intracellular signaling pathways. It is important to note that our experimental results have revealed a close TRPV6/Lck association in Jurkat cell microdomains, which was disrupted after MβCD treatment (Bobkov et al, 2021). Our data is fully consistent with studies which have shown that tyrosine phosphorylation by Src is responsible for TRPV6 activation (Sternfeld et al, 2007).…”

Section: Engagement Of Sfks In Trp Channel Phosphorylationsupporting

confidence: 92%

Impact of lipid rafts on transient receptor potential channel activities

Bobkov

Semenova

2022

Journal Cellular Physiology

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Members of the transient receptor potential (TRP) superfamily are cation channels that are expressed in nearly every mammalian cell type and respond as cellular sensors to various environmental stimuli. Light, pressure, osmolarity, temperature, and other stimuli can induce TRP calcium conductivity and correspondingly trigger many signaling processes in cells. Disruption of TRP channel activity, as a rule, harms cellular function. Despite numerous studies, the mechanisms of TRP channel regulation are not yet sufficiently clear, in part, because TRP channels are regulated by a broad set of ligands having diverse physical and chemical features. It is now known that some TRP members are located in membrane microdomains termed lipid rafts. Moreover, interaction between specific raft‐associated lipids with channels may be a key regulation mechanism. This review examines recent findings related to the roles of lipid rafts in regulation of TRP channel activity. The mechanistic events of channel interactions with the main lipid raft constituent, cholesterol, are being clarified. Better understanding of mechanisms behind such interactions would help establish the key elements of TRP channel regulation and hence allow control of cellular responses to environmental stimuli.

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Section: Engagement Of Sfks In Trp Channel Phosphorylationsupporting

confidence: 92%

Impact of lipid rafts on transient receptor potential channel activities

Bobkov

Semenova

2022

Journal Cellular Physiology

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“…Thus, it seems possible that those lipids bound under natural conditions has been shown to be, at least in parts, replaced in the excess of CHS [ 32 ]. Yet, consistent with possible binding sites of cholesterol within the channel, there are also functional data indicating that in Jurkat T cells, TRPV6 activity is sensitive to the depletion of this specific lipid [ 33 , 34 ]. Apart from cholesterol, different functional approaches point to phosphatidylinositol-4,5-bisphosphate (PIP 2 ) as an important regulator of TRPV6 and that specific channel characteristics are dependent on the levels of this lipid [ 35 , 36 , 37 , 38 , 39 , 40 , 41 ].…”

Section: Introductionmentioning

confidence: 85%

TRPV6 Regulation by Cis-22a and Cholesterol

et al. 2022

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The highly calcium-selective transient receptor potential vanilloid-type channel TRPV6 is important for epithelial Ca2+ transport. Proper regulation of the inherently constitutively active TRPV6 channels is intricate in preserving Ca2+ homeostasis, whereby structural and functional data suggest that lipids hold an essential role. Altered expression levels or specific TRPV6 mutations may lead to diseases, hence, TRPV6 represents an interesting target for pharmacological modulation. Recent cryo-EM data identified that the specific TRPV6 blocker cis-22a binds, apart from the pore, to a site within the tetrameric channel that largely matches a lipid binding pocket, LBS-2. Therein, cis-22a may replace a lipid such as cholesterol that is bound in the open state. Based on site-directed mutagenesis and functional recordings, we identified and characterized a series of residues within LBS-2 that are essential for TRPV6 inhibition by cis-22a. Additionally, we investigated the modulatory potential of diverse cholesterol depletion efforts on TRPV6 activity. While LBS-2 mutants exhibited altered maximum currents, slow Ca2+-dependent inactivation (SCDI) as well as less inhibition by cis-22a, TRPV6 activity was resistant to cholesterol depletion. Hence, lipids other than cholesterol may predominate TRPV6 regulation when the channel is expressed in HEK293 cells.

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“…Although it is not entirely clear whether the sorting process is actively mediated by lipid rafts, the partial depletion of lipid raft/ caveolae components results in receptor mis-sorting [118,[126][127][128]. The LR-mediated pathway is parallel to the degradation and recycling pathway, due to the fact that lipid rafts sort different cargoes and do not interact with Retromer/Retriever or ESCRT [129].…”

Section: Lipid Raftsmentioning

confidence: 99%

Deliver on Time or Pay the Fine: Scheduling in Membrane Trafficking

Placidi

Campa

2021

IJMS

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Membrane trafficking is all about time. Automation in such a biological process is crucial to ensure management and delivery of cellular cargoes with spatiotemporal precision. Shared molecular regulators and differential engagement of trafficking components improve robustness of molecular sorting. Sequential recruitment of low affinity protein complexes ensures directionality of the process and, concomitantly, serves as a kinetic proofreading mechanism to discriminate cargoes from the whole endocytosed material. This strategy helps cells to minimize losses and operating errors in membrane trafficking, thereby matching the appealed deadline. Here, we summarize the molecular pathways of molecular sorting, focusing on their timing and efficacy. We also highlight experimental procedures and genetic approaches to robustly probe these pathways, in order to guide mechanistic studies at the interface between biochemistry and quantitative biology.

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Lipid raft integrity is required for human leukemia Jurkat T-cell migratory activity

Cited by 11 publications

References 51 publications

Impact of lipid rafts on transient receptor potential channel activities

Impact of lipid rafts on transient receptor potential channel activities

TRPV6 Regulation by Cis-22a and Cholesterol

Deliver on Time or Pay the Fine: Scheduling in Membrane Trafficking

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