The Paralemmin Protein Family: Identification of Paralemmin-2, an Isoform Differentially Spliced to AKAP2/AKAP-KL, and of Palmdelphin, a More Distant Cytosolic Relative

Hu, Bin; Copeland, Neal G.; Gilbert, Debra J.; Jenkins, Nancy A.; Kilimann, Manfred W.

doi:10.1006/bbrc.2001.5329

Cited by 36 publications

(41 citation statements)

References 8 publications

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“…7b, 10e). An association also of intracellular paralemmin-1 with membranous or particulate structures is in line with the observation that paralemmin-1 sediments almost completely at 100,000 £ g (Kutzleb et al 1998;Hu et al 2001). An association with membrane lipid microdomains ("rafts") through its C-terminal lipid anchor is a possible explanation for the discontinuous distribution of paralemmin-1 along plasma membranes.…”

Section: Polarized Localization Of Paralemmin-1 In Adrenal Chromayn Csupporting

confidence: 86%

“…Palmdelphin, on the other hand, shares more sequence motifs with paralemmin-1 than does paralemmin-3, but the C-terminal lipidation motif is replaced by an unrelated sequence. Accordingly, palmdelphin behaves as a predominantly cytosolic protein in subcellular fractionation (Hu et al 2001), and no plasma membrane association was seen in immunomorphology (Hu et al 2005). However, immunoelectron microscopy in the brain demonstrated a spotted pattern of distribution in the cytoplasm of neuronal cell bodies and dendrites, including spines (Hu et al 2005), which is very similar to that of paralemmin-1.…”

Section: Discussionmentioning

confidence: 94%

“…The paralemmin protein family comprises four members (Hu et al 2001). The isoform, paralemmin-2, is partially expressed, by transcriptional read-through and diVerential splicing, as an unusual natural fusion protein with an "A-kinase anchor protein" (AKAP2/ AKAP-KL) encoded by a downstream gene.…”

Section: Introductionmentioning

confidence: 99%

“…Paralemmin-3, Wrst described in Xenopus laevis as Xlgv7/ Xlcaax-1, has been implicated in the diVerentiation or morphogenesis of epithelia (Cornish et al 1992). The fourth family member, palmdelphin, lacks the C-terminal lipid anchor with which the other three isoforms are endowed and is largely cytosolic (Hu et al 2001(Hu et al , 2005. In the expressed sequence tag database, paralemmin-1 and palmdelphin cDNAs are of similar frequencies, whereas paralemmin-2 and paralemmin-3 are one order of magnitude less abundant.…”

Section: Introductionmentioning

confidence: 99%

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Cellular and subcellular localization of paralemmin-1, a protein involved in cell shape control, in the rat brain, adrenal gland and kidney

Kutzleb

Petrasch‐Parwez

Kilimann

2006

Histochem Cell Biol

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Paralemmin-1 is a phosphoprotein, lipid-anchored to the cytoplasmic face of membranes and implicated in plasma membrane dynamics and cell process formation. We report an immunoperoxidase histochemical analysis of the cellular and subcellular localization of paralemmin-1 in the rat tissues where its expression is highest: the brain, the adrenal gland and the kidney. Paralemmin-1 is detected throughout the brain, in neuronal perikarya, axons and dendrites including dendritic spines and also in glial processes. In the adrenal gland, paralemmin-1 is highly expressed in the medulla. The kidney displays a pattern of differential paralemmin-1 expression in various structures and cell types, with high concentrations in cells of the parietal epithelium of Bowman's capsule, intermediate tubules, distal tubules and principal cells of outer medullary collecting ducts. Mosaics of paralemmin-positive and paralemmin-negative cells are observed in proximal tubules, the parietal epithelium of Bowman's capsule and the endothelium of many blood vessels. Plasma membrane association in epithelia is often polarized: paralemmin-1 concentrates at the apical membranes of adrenal chromaffin cells, but at the basolateral plasma membranes of proximal and distal tubule cells in the kidney. Paralemmin-1 immunoreactivity exhibits a spotted pattern and can be seen both at plasma membranes and within the cytoplasm, where it is often associated with endomembranes. This discontinuous distribution and the detergent extraction properties of paralemmin-1 suggest an association with lipid microdomains. The findings are consistent with a role for paralemmin-1 in the formation and stabilization of plasma membrane elaborations, in neurons as well as in other cell types.

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Section: Polarized Localization Of Paralemmin-1 In Adrenal Chromayn Csupporting

confidence: 86%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cellular and subcellular localization of paralemmin-1, a protein involved in cell shape control, in the rat brain, adrenal gland and kidney

Kutzleb

Petrasch‐Parwez

Kilimann

2006

Histochem Cell Biol

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“…The up-regulation of this gene upon MS-275 treatment may reflect the potential of the compound to induce differentiation in tumor cells and could serve as a differentiation and response biomarker for MS-275. Little is known about PALM2-AKAP2 (46). The corresponding mRNA is a naturally occurring cotranscribed product of the adjacent PALM2 and AKAP2 genes but the significance of this co-transcribed mRNA and the function of its putative protein product have not yet been determined.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of MS-275, a selective inhibitor of class I histone deacetylases, in human colon cancer models

Bracker

Sommer²,

Fichtner³

et al. 2009

Int J Oncol

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Abstract. N-(2-aminophenyl)-4-[N-(pyridine-3yl-methoxycarbonyl) aminomethyl] benzamide (MS-275) is a second generation histone deacetylase (HDAC) inhibitor with significant anti-tumor efficacy currently in clinical development. We investigated the effect of MS-275 treatment on various colon cancer cell lines, as well as on mouse xenograft models derived from human colorectal cancer. MS-275 exerted strong anti-proliferative effects in five cell lines and increased the acetylation of histones 3 and 4. In vivo testing of the compound in eight different models of human colon cancer derived from primary colorectal cancers or from established cell lines revealed that five models were responders, two non-responders and one an anti-responder. Gene expression profiles were determined in order to identify genes and pathways differentially regulated upon MS-275 treatment in responder versus non-responder models. Principle component analysis revealed a correlation of the anti-tumor efficacy with the sub-clustering of the MS-275 treatment groups in 7 out of 8 models. Although the overall gene expression pattern was rather unique for each individual model, 129 genes were significantly up-and 58 genes significantly down-regulated in at least 2 out of 5 responder models in response to MS-275 treatment. We identified potential biomarkers for response to MS-275, such as PRA1, MYADM and PALM2-AKAP2 which were up-regulated in all responder models and downregulated or unchanged in all non-responder models. Our results provide a starting point for the development of clinically relevant biomarkers for predicting a response to MS-275 and the understanding of the mode of action of this HDAC inhibitor.

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APOE ε4–associated downregulation of the IL‐7/IL‐7R pathway in effector memory T cells: Implications for Alzheimer's disease

Zhang,

Cheng,

Tang

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONThe apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive.METHODSThe present study enrolled 54 patients diagnosed with late‐onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non‐carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA‐seq) and single‐cell RNA sequencing (scRNA‐seq) analysis of peripheral blood mononuclear cells (PBMCs).RESULTSPlasma tumor necrosis factor α, interferon γ, and interleukin (IL)‐33 levels increased in the APOE ε4 carriers but IL‐7 expression notably decreased. A negative correlation was observed between plasma IL‐7 level and the hippocampal atrophy degree. Additionally, the expression of IL‐7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA‐seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells.DISCUSSIONThese findings shed light on the role of the downregulated IL‐7/IL‐7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy.Highlights The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)‐7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL‐7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL‐7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL‐7/IL‐7R signal pathways enriches T cells.

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The Paralemmin Protein Family: Identification of Paralemmin-2, an Isoform Differentially Spliced to AKAP2/AKAP-KL, and of Palmdelphin, a More Distant Cytosolic Relative

Cited by 36 publications

References 8 publications

Cellular and subcellular localization of paralemmin-1, a protein involved in cell shape control, in the rat brain, adrenal gland and kidney

Cellular and subcellular localization of paralemmin-1, a protein involved in cell shape control, in the rat brain, adrenal gland and kidney

Efficacy of MS-275, a selective inhibitor of class I histone deacetylases, in human colon cancer models

APOE ε4–associated downregulation of the IL‐7/IL‐7R pathway in effector memory T cells: Implications for Alzheimer's disease

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