PRALINETM: a strategy for improved multiple alignment of transmembrane proteins

VMP1 and DedA proteins are conserved families of transmembrane proteins in eukaryotes and prokaryotes respectively. Despite numerous reports involving these proteins in multiple cellular processes, their molecular function is still unknown. They share the domain of unknown function PF09335, suggesting a possible functional relationship between these protein families. Here we show that VMP1 from different species contain two short motifs conserved in the bacterial DedA proteins and the yeast protein Tvp38. The hallmark of one of these motifs is a glycine residue previously shown to be strictly conserved in all the DedA proteins. Substitution of this residue to leucine, glutamate or arginine in Dictyostelium Vmp1 inactivates the protein, as shown by the inability of the mutants to rescue the phenotypes associated with the lack of Vmp1 including development and lipid homeostasis. This is the first experimental approach that supports an evolutionary relationship between Vmp1 and DedA proteins and highlights the importance of the conserved glycine residue in the PF09335 domain.

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Aggregation of myocardial sarcolemmal transmembrane proteins is not hindered by an interaction with the cytoskeleton. Possible implications for ischemia and reperfusion

Journal of Molecular and Cellular Cardiology ◽

10.1016/s0022-2828(95)91947-3 ◽

1995 ◽

Vol 27 (10) ◽

pp. 2337-2345 ◽

Cited By ~ 3

Author(s):

Chris T.W.M. Schneijdenberg ◽

Arie J. Verkleij ◽

Jan A. Post

Keyword(s):

Transmembrane Proteins ◽

Ischemia And Reperfusion

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A family of pathogen-induced cysteine-rich transmembrane proteins is involved in plant disease resistance

Planta ◽

10.1007/s00425-021-03606-3 ◽

2021 ◽

Vol 253 (5) ◽

Author(s):

Marciel Pereira Mendes ◽

Richard Hickman ◽

Marcel C. Van Verk ◽

Nicole M. Nieuwendijk ◽

Anja Reinstädler ◽

...

Keyword(s):

Arabidopsis Thaliana ◽

Plasma Membrane ◽

Disease Resistance ◽

Plant Disease Resistance ◽

Transmembrane Proteins ◽

Series Data ◽

Immune Gene ◽

Biological Processes ◽

Hypocotyl Growth ◽

Enhanced Resistance

Abstract Main conclusion Overexpression of pathogen-induced cysteine-rich transmembrane proteins (PCMs) in Arabidopsis thaliana enhances resistance against biotrophic pathogens and stimulates hypocotyl growth, suggesting a potential role for PCMs in connecting both biological processes. Abstract Plants possess a sophisticated immune system to protect themselves against pathogen attack. The defense hormone salicylic acid (SA) is an important player in the plant immune gene regulatory network. Using RNA-seq time series data of Arabidopsis thaliana leaves treated with SA, we identified a largely uncharacterized SA-responsive gene family of eight members that are all activated in response to various pathogens or their immune elicitors and encode small proteins with cysteine-rich transmembrane domains. Based on their nucleotide similarity and chromosomal position, the designated Pathogen-induced Cysteine-rich transMembrane protein (PCM) genes were subdivided into three subgroups consisting of PCM1-3 (subgroup I), PCM4-6 (subgroup II), and PCM7-8 (subgroup III). Of the PCM genes, only PCM4 (also known as PCC1) has previously been implicated in plant immunity. Transient expression assays in Nicotiana benthamiana indicated that most PCM proteins localize to the plasma membrane. Ectopic overexpression of the PCMs in Arabidopsis thaliana resulted in all eight cases in enhanced resistance against the biotrophic oomycete pathogen Hyaloperonospora arabidopsidis Noco2. Additionally, overexpression of PCM subgroup I genes conferred enhanced resistance to the hemi-biotrophic bacterial pathogen Pseudomonas syringae pv. tomato DC3000. The PCM-overexpression lines were found to be also affected in the expression of genes related to light signaling and development, and accordingly, PCM-overexpressing seedlings displayed elongated hypocotyl growth. These results point to a function of PCMs in both disease resistance and photomorphogenesis, connecting both biological processes, possibly via effects on membrane structure or activity of interacting proteins at the plasma membrane.

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Neuron–Glia Interactions in Tuberous Sclerosis Complex Affect the Synaptic Balance in 2D and Organoid Cultures

Cells ◽

10.3390/cells10010134 ◽

2021 ◽

Vol 10 (1) ◽

pp. 134

Author(s):

Stephanie Dooves ◽

Arianne J. H. van Velthoven ◽

Linda G. Suciati ◽

Vivi M. Heine

Keyword(s):

Tuberous Sclerosis ◽

Glial Cells ◽

Tuberous Sclerosis Complex ◽

Neuronal Development ◽

Transmembrane Proteins ◽

Significant Burden ◽

Epidermal Growth ◽

And Control ◽

Egf Signaling ◽

The Brain

Tuberous sclerosis complex (TSC) is a genetic disease affecting the brain. Neurological symptoms like epilepsy and neurodevelopmental issues cause a significant burden on patients. Both neurons and glial cells are affected by TSC mutations. Previous studies have shown changes in the excitation/inhibition balance (E/I balance) in TSC. Astrocytes are known to be important for neuronal development, and astrocytic dysfunction can cause changes in the E/I balance. We hypothesized that astrocytes affect the synaptic balance in TSC. TSC patient-derived stem cells were differentiated into astrocytes, which showed increased proliferation compared to control astrocytes. RNA sequencing revealed changes in gene expression, which were related to epidermal growth factor (EGF) signaling and enriched for genes that coded for secreted or transmembrane proteins. Control neurons were cultured in astrocyte-conditioned medium (ACM) of TSC and control astrocytes. After culture in TSC ACM, neurons showed an altered synaptic balance, with an increase in the percentage of VGAT+ synapses. These findings were confirmed in organoids, presenting a spontaneous 3D organization of neurons and glial cells. To conclude, this study shows that TSC astrocytes are affected and secrete factors that alter the synaptic balance. As an altered E/I balance may underlie many of the neurological TSC symptoms, astrocytes may provide new therapeutic targets.

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