scholarly journals A palmitoylation code controls PI4KIIIα complex formation and PI(4,5)P2 homeostasis at the plasma membrane

2021 ◽  
Author(s):  
Alex G. Batrouni ◽  
Nirmalya Bag ◽  
Henry Phan ◽  
Barbara A. Baird ◽  
Jeremy M. Baskin
Keyword(s):  
Plasma Membrane ◽  
Complex Formation ◽  
Biosynthetic Pathway ◽  
Transmembrane Protein ◽  
Lipid Kinase ◽  
Lipid Interactions ◽  
Liquid Ordered ◽  
Disordered Regions

PI4KIIIα is the major enzyme responsible for generating the phosphoinositide PI(4)P at the plasma membrane. This lipid kinase forms two multicomponent complexes, both including a palmitoylated anchor, EFR3. Whereas both PI4KIIIα complexes support production of PI(4)P, the distinct functions of each complex and mechanisms underlying the interplay between them remain unknown. Here, we present roles for differential palmitoylation patterns within a tri-Cys motif in EFR3B (Cys5/Cys7/Cys8) in controlling the distribution of PI4KIIIα between these two complexes at the plasma membrane and corresponding functions in phosphoinositide homeostasis. Spacing of palmitoyl groups within three doubly palmitoylated EFR3B “lipoforms” affects both its interactions with TMEM150A, a transmembrane protein governing formation of a PI4KIIIα complex functioning in rapid PI(4,5)P2 resynthesis following PLC signaling, and its partitioning within liquid-ordered and -disordered regions of the plasma membrane. This work identifies a palmitoylation code in controlling protein-protein and protein-lipid interactions affecting a plasma membrane-resident lipid biosynthetic pathway.

scholarly journals A palmitoylation code controls PI4KIIIα complex formation and PI(4,5)P2 homeostasis at the plasma membrane

2021 ◽  
Author(s):  
Alex G Batrouni ◽  
Nirmalya Bag ◽  
Henry Phan ◽  
Barbara A Baird ◽  
Jeremy M Baskin
Keyword(s):  
Plasma Membrane ◽  
Complex Formation ◽  
Biosynthetic Pathway ◽  
Transmembrane Protein ◽  
Lipid Kinase ◽  
Lipid Interactions ◽  
Liquid Ordered ◽  
Disordered Regions

PI4KIIIα is the major enzyme responsible for generating the phosphoinositide PI(4)P at the plasma membrane. This lipid kinase forms two multicomponent complexes, both including a palmitoylated anchor, EFR3. Whereas both PI4KIIIα complexes support production of PI(4)P, the distinct functions of each complex and mechanisms underlying the interplay between them remain unknown. Here, we present roles for differential palmitoylation patterns within a tri-Cys motif in EFR3B (Cys5/Cys7/Cys8) in controlling the distribution of PI4KIIIα between these two complexes at the plasma membrane and corresponding functions in phosphoinositide homeostasis. Spacing of palmitoyl groups within three doubly palmitoylated EFR3B "lipoforms" affects both its interactions with TMEM150A, a transmembrane protein governing formation of a PI4KIIIα complex functioning in rapid PI(4,5)P2 resynthesis following PLC signaling, and its partitioning within liquid-ordered and -disordered regions of the plasma membrane. This work identifies a palmitoylation code in controlling protein-protein and protein-lipid interactions affecting a plasma membrane-resident lipid biosynthetic pathway.

scholarly journals High-speed single-molecule imaging reveals signal transduction by induced transbilayer raft phases

2020 ◽  
Vol 219 (12) ◽  
Author(s):  
Ikuko Koyama-Honda ◽  
Takahiro K. Fujiwara ◽  
Rinshi S. Kasai ◽  
Kenichi G.N. Suzuki ◽  
Eriko Kajikawa ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Single Molecule ◽  
High Speed ◽  
Transmembrane Protein ◽  
Single Molecule Imaging ◽  
Lipid Interactions ◽  
Alkyl Chains ◽  
Outer Leaflet ◽  
Protein Moiety

Using single-molecule imaging with enhanced time resolutions down to 5 ms, we found that CD59 cluster rafts and GM1 cluster rafts were stably induced in the outer leaflet of the plasma membrane (PM), which triggered the activation of Lyn, H-Ras, and ERK and continually recruited Lyn and H-Ras right beneath them in the inner leaflet with dwell lifetimes <0.1 s. The detection was possible due to the enhanced time resolutions employed here. The recruitment depended on the PM cholesterol and saturated alkyl chains of Lyn and H-Ras, whereas it was blocked by the nonraftophilic transmembrane protein moiety and unsaturated alkyl chains linked to the inner-leaflet molecules. Because GM1 cluster rafts recruited Lyn and H-Ras as efficiently as CD59 cluster rafts, and because the protein moieties of Lyn and H-Ras were not required for the recruitment, we conclude that the transbilayer raft phases induced by the outer-leaflet stabilized rafts recruit lipid-anchored signaling molecules by lateral raft–lipid interactions and thus serve as a key signal transduction platform.

scholarly journals High-speed single-molecule imaging reveals signal transduction by induced transbilayer raft phases

2020 ◽  
Author(s):  
Ikuko Koyama-Honda ◽  
Takahiro K. Fujiwara ◽  
Rinshi S. Kasai ◽  
Kenichi G. N. Suzuki ◽  
Eriko Kajikawa ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Single Molecule ◽  
High Speed ◽  
Transmembrane Protein ◽  
Single Molecule Imaging ◽  
Lipid Interactions ◽  
Alkyl Chains ◽  
Outer Leaflet ◽  
Protein Moiety

AbstractUsing single-molecule imaging with enhanced time resolutions down to 5 ms, we found that CD59-cluster rafts and GM1-cluster rafts stably induced in the outer leaflet of the plasma membrane (PM), which triggered the activation of Lyn, H-Ras, and ERK, continually recruited Lyn and H-Ras right beneath them in the inner leaflet, with dwell lifetimes of <0.1 s. The detection was possible due to the enhanced time resolutions employed here. The recruitment depended on the PM cholesterol and saturated alkyl chains of Lyn and H-Ras, whereas it was blocked by the non-raftophilic transmembrane protein moiety and unsaturated alkyl chains linked to the inner-leaflet molecules. Since GM1-cluster rafts recruited Lyn and H-Ras as efficiently as CD59-cluster rafts, and the protein moieties of Lyn and H-Ras were not required for the recruitment, we conclude that the transbilayer raft phases induced by the outer-leaflet stabilized rafts recruit lipid-anchored signaling molecules by lateral raft-lipid interactions, and thus serve as a key signal transduction platform.SummaryHigh-speed single-molecule imaging indicated that CD59-cluster rafts and GM1-cluster rafts stably induced in the plasma membrane outer leaflet generated nano-scale transbilayer raft phases, which continually and transiently recruited Lyn and H-Ras in the inner leaflet by cooperative raft-lipid interactions.

scholarly journals Lateral diffusion of wild-type and mutant Ld antigens in L cells.

1984 ◽  
Vol 99 (6) ◽  
pp. 2333-2335 ◽  
Author(s):  
M Edidin ◽  
M Zuniga
Keyword(s):  
Plasma Membrane ◽  
Diffusion Coefficients ◽  
Transmembrane Protein ◽  
Transmembrane Proteins ◽  
Lateral Diffusion ◽  
Cytoplasmic Domain ◽  
Histocompatibility Antigen ◽  
Wild Type ◽  
Major Histocompatibility Antigen ◽  
Cytoplasmic Side

We have compared the lateral diffusion of intact transmembrane proteins, wild-type H-2Ld antigens, with that of mutants truncated in the cytoplasmic domain. Diffusion coefficients and mobile fractions were similar for all molecules examined, from wild-type Ld antigens with 31 residues on the cytoplasmic side of the plasma membrane to mutants with only four residues in the cytoplasmic domain. This result limits ways in which the lateral diffusion of a major histocompatibility antigen, a transmembrane protein, can be constrained by interactions with other molecules.

scholarly journals Structural basis for cholesterol transport-like activity of the Hedgehog receptor Patched

2018 ◽  
Author(s):  
Yunxiao Zhang ◽  
David P. Bulkley ◽  
Kelsey J. Roberts ◽  
Yao Xin ◽  
Daniel E. Asarnow ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Extracellular Domain ◽  
Structural Basis ◽  
Cholesterol Transport ◽  
Common Cause ◽  
Common Receptor

AbstractHedgehog protein signals mediate tissue patterning and maintenance via binding to and inactivation of their common receptor Patched, a twelve-transmembrane protein that otherwise would suppress activity of the seven-transmembrane protein, Smoothened. Loss of Patched function, the most common cause of basal cell carcinoma, permits unregulated activation of Smoothened and of the Hedgehog pathway. A cryo-EM structure of the Patched protein reveals striking transmembrane domain similarities to prokaryotic RND transporters. The extracellular domain mediates association of Patched monomers in an unusual dimeric architecture that implies curvature in the associated membrane. A central conduit with cholesterol-like contents courses through the extracellular domain and resembles that used by other RND proteins to transport substrates, suggesting Patched activity in cholesterol transport. Patched expression indeed reduces cholesterol activity in the inner leaflet of the plasma membrane, in a manner antagonized by Hedgehog stimulation and with implications for regulation of Smoothened.

scholarly journals Proteomic Analysis of the Function of a Novel Cold-Regulated Multispanning Transmembrane Protein COR413-PM1 in Arabidopsis

2018 ◽  
Vol 19 (9) ◽  
pp. 2572 ◽  
Author(s):  
Chen Su ◽  
Kai Chen ◽  
Qingqian Ding ◽  
Yongying Mou ◽  
Rui Yang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Plasma Membrane ◽  
Fatty Acid ◽  
Proteomic Analysis ◽  
Fatty Acid Biosynthesis ◽  
Transmembrane Protein ◽  
Sugar Metabolism ◽  
Freezing Stress ◽  
Plant Tolerance ◽  
Phosphoribosyl Pyrophosphate

The plasma membrane is the first subcellular organ that senses low temperature, and it includes some spanning transmembrane proteins that play important roles in cold regulation. COR413-PM1 is a novel multispanning transmembrane cold-regulated protein; however, the related functions are not clear in Arabidopsis. We found the tolerance to freezing stress of cor413-pm1 was lower than wild-type (WT). A proteomics method was used to analyze the differentially abundant proteins (DAPs) between cor413-pm1 and WT. A total of 4143 protein groups were identified and 3139 were accurately quantitated. The DAPs associated with COR413-PM1 and freezing treatment were mainly involved in the metabolism of fatty acids, sugars, and purine. Quantitative real-time PCR (qRT-PCR) confirmed the proteomic analysis results of four proteins: fatty acid biosynthesis 1 (FAB1) is involved in fatty acid metabolism and might affect the plasma membrane structure; fructokinase 3 (FRK3) and sucrose phosphate synthase A1 (SPSA1) play roles in sugar metabolism and may influence the ability of osmotic adjustment under freezing stress; and GLN phosphoribosyl pyrophosphate amidotransferase 2 (ASE2) affects freezing tolerance through purine metabolism pathways. In short, our results demonstrate that the multispanning transmembrane protein COR413-PM1 regulates plant tolerance to freezing stress by affecting the metabolism of fatty acids, sugars, and purine in Arabidopsis.

Plasma membrane localization of the Toll protein in the syncytial Drosophila embryo: importance of transmembrane signaling for dorsal-ventral pattern formation

Development ◽  
1991 ◽  
Vol 111 (4) ◽  
pp. 1021-1028 ◽  
Author(s):  
C. Hashimoto ◽  
S. Gerttula ◽  
K.V. Anderson
Keyword(s):  
Plasma Membrane ◽  
Cell Adhesion ◽  
Transmembrane Protein ◽  
Drosophila Embryo ◽  
Membrane Localization ◽  
Transmembrane Signaling ◽  
Perivitelline Space ◽  
Cell Surfaces ◽  
Plasma Membrane Localization ◽  
Promote Cell Adhesion

Formation of the Drosophila embryo's dorsal-ventral pattern requires the maternal product of the Toll gene. DNA sequence and genetic analyses together suggested that the Toll gene product is a transmembrane protein which communicates information from an extracytoplasmic compartment to the cytoplasm. Using antibodies as probes, we show that the Toll protein is a 135 × 10(3) Mr glycoprotein which is tightly associated with embryonic membranes. During the syncytial stage when dorsal-ventral polarity is established, the maternal Toll protein is associated with the plasma membrane around the entire embryo. During later embryonic stages, the Toll protein is expressed zygotically on many cell surfaces, possibly to promote cell adhesion. The plasma membrane localization of the Toll protein in the syncytial embryo suggests that transmembrane signaling from the extracellular perivitelline space to the cytoplasm is required for establishment of the embryonic dorsal-ventral pattern.

Disorders of Thiamine Metabolism

2016 ◽  
Author(s):  
Frédéric Sedel ◽  
Carla E. M. Hollak
Keyword(s):  
Plasma Membrane ◽  
Biosynthetic Pathway ◽  
Megaloblastic Anemia ◽  
Active Form ◽  
Pentose Phosphate ◽  
Water Soluble ◽  
Thiamine Pyrophosphate ◽  
Disease Mutations ◽  
Water Soluble Vitamin ◽  
Basal Ganglia Disease

Thiamine is a water-soluble vitamin acting in the mitochondria as a cofactor for energy metabolism and, in the cytoplasm, in the pentose phosphate biosynthetic pathway. Its transport through the plasma membrane requires two transporters with overlapping functions: THTR1 encoded by SLC19A2, and THTR2 encoded by SLC19A3. Thiamine is transformed into its active form, thiamine pyrophosphate (TPP) by a kinase encoded by the TPK1 gene. Then it may enter the mitochondria through a TPP transporter encoded by SLC25A19. Mutations in SLC19A2 cause thiamine-responsive megaloblastic anemia (TRMA). Mutations in SLC19A3 cause biotin/thiamine–responsive basal ganglia disease. Mutations in SLC25A19 may cause early microcephaly with death in infancy (also called Amish microcephaly) or a later-onset bilateral striatal necrosis with progressive peripheral neuropathy. Recently, mutations in the TPK1 gene have been associated with recurrent encephalopathy with mild lactic acidosis.

Sign in / Sign up

Export Citation Format

Share Document