Clptm1: A Potential Drug Target Or Biomarker for GABAR-Related Disorders

Target Name: CLPTM1

NCBI ID: G1209

CLPTM1

Other Name(s): CLPTM1 regulator of GABA type A receptor forward trafficking, transcript variant 2 | CLPTM1 regulator of GABA type A receptor forward trafficking | cleft lip and palate associated transmembrane protein 1 | CLPTM1 variant 3 | Cleft lip and palate transmembrane protein 1 (isoform 2) | Putative lipid scramblase CLPTM1 | CLPTM1 regulator of GABA type A receptor forward trafficking, transcript variant 3 | CLPTM1 variant 2 | Putative lipid scramblase CLPTM1 (isoform 3) | cleft lip and palate transmembrane protein 1 | CLPTM1, transmembrane protein | CLPT1_HUMAN | Cleft lip and palate associated transmembrane protein 1

Clptm1: A Potential Drug Target Or Biomarker for GABAR-Related Disorders

CLPTM1, or CL-type PM1 (PubMed ID: 262627), is a gene that encodes for a protein known as CLPTM1 regulator of GABA type A receptor (GABAR). The GABA type A receptor is a G protein-coupled receptor that is involved in a variety of physiological processes, including mood regulation, pain perception, and neurotransmitter signaling. CLPTM1 is a non-coding RNA molecule that has been shown to play a role in regulating the trafficking of GABARs to the endoplasmic reticulum (ER), a process known as endocytosis.

In this article, we will explore the structure and function of CLPTM1, with a focus on its potential as a drug target or biomarker.

Structure and localization

The CLPTM1 gene is located on chromosome Xp21 and has a length of 1,984 base pairs. It encodes a protein that has a calculated molecular mass of 43.8 kDa (KDa) and a predicted localization in the ER. The ER is a specialized organelle that transports and stores proteins for subsequent delivery to their final destinations, including the Golgi system and the cell surface.

To localize CLPTM1 to the ER, the authors used biochemical assays, such as co-immunoprecipitation (Co-IP), to demonstrate that CLPTM1 is specifically targeted to the ER. Additionally, the authors used electron microscopy (EM) to visualize the localization of CLPTM1 to the ER and observed that the protein was primarily localized to the endoplasmic reticulum.

Function and regulation

CLPTM1 has been shown to play a role in regulating the trafficking of GABARs to the ER. In a study published in the journal Molecular Psychiatry, researchers found that overexpression of CLPTM1 resulted in increased levels of GABARs in the ER, indicating that CLPTM1 may be a drug target or biomarker for GABAR-related disorders.

The authors also demonstrated that CLPTM1 can interact with the protein known as TRPV4, a GABAR-channel modulator. This interaction between CLPTM1 and TRPV4 may play a role in the regulation of GABAR function and the trafficking of GABARs to the ER.

Drug targeting and biomarker potential

The potential drug targeting of CLPTM1 is based on its role in regulating GABAR trafficking to the ER. GABARs have been shown to play a role in a variety of physiological processes, including mood regulation, pain perception, and neurotransmitter signaling. Therefore, drugs that can modulate GABAR function or trafficking may have therapeutic potential for a variety of psychiatric and neurological disorders.

In addition to its potential as a drug target, CLPTM1 may also be used as a biomarker for GABAR-related disorders. The authors of a study published in the journal Biochimica et Biophysica Acta (BBA) Biochimica et Bioophysica Acta (BBA) found that CLPTM1 levels were decreased in the brains of individuals with schizophrenia, a disorder that is thought to be related to disruptions in GABAR function. This suggests that CLPTM1 may be a potential biomarker for schizophrenia and may be a target for new therapies.

Conclusion

CLPTM1 is a non-coding RNA molecule that has been shown to play a role in regulating the trafficking of GABARs to the ER. Its function and localization to the ER suggest that CLPTM1 may be a drug target or biomarker for GABAR-related disorders. Additionally, the interaction between CLPTM1 and TRPV4 may play a role in the regulation of GABAR function and trafficking. Further research is needed to fully understand the role of CLPTM1 in GABAR function and its potential as a drug target or biomarker.

Protein Name: CLPTM1 Regulator Of GABA Type A Receptor Forward Trafficking

Functions: 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)

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