CLPTM1

Last update 08 May 2025

Basic Info

Synonyms

Cleft lip and palate transmembrane protein 1, CLPTM1, CLPTM1 regulator of GABA type A receptor forward trafficking

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Introduction

Involved in GABAergic but not glutamatergic transmission. Binds and traps GABAA receptors in the endoplasmic reticulum (ER). Modulates postsynaptic GABAergic transmission, and therefore inhibitory neurotransmission, by reducing the plasma membrane expression of these receptors. Altered GABAergic signaling is one among many causes of cleft palate (By similarity). Might function as a lipid scramblase, translocating lipids in membranes from one leaflet to the other one (By similarity). Required for efficient glycosylphosphatidylinositol (GPI) inositol deacylation in the ER, which is a crucial step to switch GPI-anchored proteins (GPI-APs) from protein folding to transport states (PubMed:29255114). May play a role in T-cell development (By similarity).

100 Clinical Results associated with CLPTM1

100 Translational Medicine associated with CLPTM1

0 Patents (Medical) associated with CLPTM1

Literatures (Medical) associated with CLPTM1

05 Feb 2025·The Journal of Biochemistry

Commentary for: a lipid scramblase TMEM41B is involved in the processing and transport of GPI-anchored proteins

Article

Author: Hirayama, Hiroto

AbstractGlycosylphosphatidylinositol (GPI) anchoring is a conserved post-translational modification in eukaryotes. This modification allows acceptor proteins to be expressed at the cell surface as GPI-anchored proteins (GPI-APs), which play critical roles in various biological processes. It has been proposed that remodelling of GPI after transferring acceptor proteins, including the PGAP1-dependent deacylation of GPI-inositol, functions as a checkpoint for transporting mature GPI-APs from the endoplasmic reticulum (ER) to the Golgi. A previous study identified several factors involved in regulating PGAP1-dependent GPI-inositol deacylation, including proteins associated with the calnexin cycles, SELT and CLPTM1. A recent report by Cao et al., revealed that the loss of TMEM41B, an ER-resident lipid scramblase, rescues the defect in GPI-inositol deacylation in SELT-KO cells. Further investigation demonstrated that TMEM41B is essential for the efficient transport of both GPI-APs and transmembrane proteins from the ER to the Golgi. The study also found that PGAP1 proteins accumulate in the ER of TMEM41B-KO cells, suggesting that perturbations in the ER-membrane lipid integrity stabilize PGAP1 proteins, thereby enhancing the PGAP1 activity within the ER. These findings highlight that defects in TMEM41B impact two distinct processes: (i) the transport of GPI-APs from the ER to the Golgi, and (ii) the deacylation of GPI-APs.

07 Aug 2024·The Journal of Neuroscience

Haploinsufficiency of GABA_AReceptor-Associated Clptm1 Enhances Phasic and Tonic Inhibitory Neurotransmission, Suppresses Excitatory Synaptic Plasticity, and Impairs Memory

Article

Author: Ge, Yuan ; Craig, Ann Marie

The mechanisms utilized by neurons to regulate the efficacy of phasic and tonic inhibition and their impacts on synaptic plasticity and behavior are incompletely understood. Cleft lip and palate transmembrane protein 1 (Clptm1) is a membrane-spanning protein that interacts with multiple γ-aminobutyric acid type A receptor (GABAAR) subunits, trapping them in the endoplasmic reticulum and Golgi network. Overexpression and knock-down studies suggest that Clptm1 modulates GABAAR-mediated phasic inhibition and tonic inhibition as well as activity-induced inhibitory synaptic homeostasis in cultured hippocampal neurons. To investigate the role of Clptm1 in the modulation of GABAARs in vivo, we generated Clptm1 knock-out (KO) mice. Here, we show that genetic KO of Clptm1 elevated phasic and tonic inhibitory transmission in both male and female heterozygous mice. Although basal excitatory synaptic transmission was not affected, Clptm1 haploinsufficiency significantly blocked high-frequency stimulation-induced long–term potentiation (LTP) in hippocampal CA3→CA1 synapses. In the hippocampus-dependent contextual fear-conditioning behavior task, both male and female Clptm1 heterozygous KO mice exhibited impairment in contextual fear memory. In addition, LTP and contextual fear memory were rescued by application of L-655,708, a negative allosteric modulator of the extrasynaptic GABAAR α5 subunit. These results suggest that haploinsufficiency of Clptm1 contributes to cognitive deficits through altered synaptic transmission and plasticity by elevation of inhibitory neurotransmission, with tonic inhibition playing a major role.

01 Jan 2024·International Journal of Legal Medicine

Candidate biomarkers in brown adipose tissue for post-mortem diagnosis of fatal hypothermia

Article

Author: Zhao, Rui ; Guan, Da-Wei ; Wang, Lin-Lin ; Wang, Zi-Wei ; Wang, Ning ; Zhang, Fu-Yuan ; Wang, Peng-Fei ; Guo, Xiang-Shen ; Zhang, Miao ; Cao, Zhi-Peng

Post-mortem diagnosis of fatal hypothermia (FHT) is challenging in forensic practice because traditional morphological and biochemical methods lack specificity. Recent studies have reported that brown adipose tissue (BAT) is activated during cold-induced non-shivering thermogenesis in mammals, but BAT has not been used to diagnose FHT. The aim of this study was to identify novel biomarkers in BAT for FHT based on morphological changes and differential protein expression. Two FHT animal models were created by exposing mice to 4 or -20 °C at 50% humidity. Morphologically, the unilocular lipid droplet content was significantly increased in BAT of FHT model mice compared with that of control mice. Proteomics analysis revealed a total of 283 and 266 differentially expressed proteins (DEPs) between the 4 or -20 °C FHT subgroups and control group, respectively. In addition, 140 proteins were shared between the FHT subgroups. GO and KEGG analyses revealed that the shared DEPs were mainly enriched in pathways associated with metabolism, oxidative phosphorylation, and thermogenesis. Further screening (|log₂FC| > 1.6, q-value (FDR) < 0.05) identified GMFB, KDM1A, DDX6, RAB1B, SHMT-1, CLPTM1, and LMF1 as candidate biomarkers of FHT. Subsequent validation experiments were performed in FHT model mice using classic immunohistochemistry and western blotting. RAB1B and GMFB expression was further verified in BAT specimens from human cases of FHT. The results demonstrate that BAT can be used as a target organ for FHT diagnosis employing RAB1B and GMFB as biological markers, thus providing a new strategy for the post-mortem diagnosis of FHT in forensic practice.

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CLPTM1

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