Calcium-modulating cyclophilin ligand regulates membrane trafficking of postsynaptic GABAA receptors

Xu, Yi; Yao, Jun; Norris, David E.; Tran, David; Bram, Richard J.; Chen, Gong; Lüscher, Bernhard

doi:10.1016/j.mcn.2008.03.002

Cited by 37 publications

(31 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, although our coprecipitation experiments with anti-CAML antibodies demonstrated that WRB is quantitatively associated with CAML, we could not carry out the reverse experiment, because there are currently no available antibodies that immunoprecipitate native WRB. It is possible that some of the many functions linked to CAML, including signal transduction (41,42), immune cell survival (26), membrane traffic (24,43), and chromosome segregation (44), are independent from its role in TA protein insertion and could be carried out by a pool of WRB-free CAML. In addition, or alternatively, the excess CAML could increase the efficiency of recruitment of TRC40-TA complexes to the ER membrane, handing them over to the CAML-WRB complex.…”

Section: Discussionmentioning

confidence: 99%

Tail-anchored Protein Insertion in Mammals

Colombo

Cardani

Maroli

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

The GET (guided entry of tail-anchored proteins)/TRC (transmembrane recognition complex) pathway for tail-anchored protein targeting to the endoplasmic reticulum (ER) has been characterized in detail in yeast and is thought to function similarly in mammals, where the orthologue of the central ATPase, Get3, is known as TRC40 or Asna1. Get3/TRC40 function requires an ER receptor, which in yeast consists of the Get1/ Get2 heterotetramer and in mammals of the WRB protein (tryptophan-rich basic protein), homologous to yeast Get1, in combination with CAML (calcium-modulating cyclophilin ligand), which is not homologous to Get2. To better characterize the mammalian receptor, we investigated the role of endogenous WRB and CAML in tail-anchored protein insertion as well as their association, concentration, and stoichiometry in rat liver microsomes and cultured cells. Functional proteoliposomes, reconstituted from a microsomal detergent extract, lost their activity when made with an extract depleted of TRC40-associated proteins or of CAML itself, whereas in vitro synthesized CAML and WRB together were sufficient to confer insertion competence to liposomes. CAML was found to be in ϳ5-fold excess over WRB, and alteration of this ratio did not inhibit insertion. Depletion of each subunit affected the levels of the other one; in the case of CAML silencing, this effect was attributable to destabilization of the WRB transcript and not of WRB protein itself. These results reveal unanticipated complexity in the mutual regulation of the TRC40 receptor subunits and raise the question as to the role of the excess CAML in the mammalian ER.Whereas most membrane proteins are targeted to the endoplasmic reticulum (ER) 3 by the signal recognition particle-dependent co-translational mechanism (1, 2), tail-anchored (TA) membrane proteins are inserted into all their target membranes, including the ER, by post-translational pathways (for review see Refs. 3-5). The inability of TA proteins to utilize the co-translational route is due to the location of their sole targeting determinant, the transmembrane domain (TMD), at their extreme C terminus, such that it becomes accessible to cytosolic targeting factors only after release of the completed polypeptide chain from the ribosome. Because TA proteins are numerous (6), play fundamental physiological roles (e.g. as SNAREs and apoptosis regulating factors; Ref.3), and are present in all domains of life (7), a great deal of research has been dedicated to the elucidation of the mechanisms by which they reach and insert into their target membranes. On the basis of studies in cell-free mammalian systems (8, 9) and of in vitro and in vivo investigations in yeast (10), a novel system operating in the delivery of TA proteins to the ER membrane was identified and extensively characterized (for review, see Refs. 11 and 12). This system is centered around a cytosolic P-type ATPase, named Get3 (guided entry of tailanchored proteins) in yeast and TRC40 (transmembrane domain recognition complex subunit of 40...

show abstract

Section: Discussionmentioning

confidence: 99%

Tail-anchored Protein Insertion in Mammals

Colombo

Cardani

Maroli

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Structurally, the C-terminus of CAML is integrated into the membrane, but most of molecule faces the cytoplasm [13,14]. This cytoplasmic portion interacts with the intracellular regions of various types of membrane-bound receptors, such as, TACI [12], epidermal growth factor receptor (EGFR) [15], mucin 1 (MUC1) [16], and GABA receptor [17]. Furthermore, functionally, CAML is involved in the signaling of these receptors.…”

Section: Introductionmentioning

confidence: 99%

CAML promotes prolactin-dependent proliferation of breast cancer cells by facilitating prolactin receptor signaling pathways

Lim

Kim

et al. 2010

Breast Cancer Res Treat

View full text Add to dashboard Cite

Calcium-modulating cyclophilin ligand (CAML) interacts with the intracellular regions of various types of membrane-bound receptors, and is required for signaling pathways that involve these receptors. The authors tested the possibility that CAML interacts with prolactin receptor (PRLR) and participates in the prolactin (PRL)-dependent proliferation of breast cancer cells. Breast cancer cell lines were found to express CAML at higher levels than cell lines originating from leukemia and other cancers. Furthermore, immunohistochemical analyses of breast tissue arrays showed that the CAML levels were higher in cancer tissues than in normal tissues. In breast cancer cells and transfected HEK293 cells, CAML associated with PRLR, and this interaction was augmented during PRL stimulation. CAML-silencing experiments revealed that CAML is required for the functions of PRLR, such as, the activations of Stat5 and Mek1/2, PRL internalization with cyclophilin B, PRLR recycling, and increased Ca(2+) mobilization. In addition, CAML was found to play a crucial role in the PRL/PRLR-dependent growth of breast cancer cells. These results suggest a new role for CAML in breast cancer development.

show abstract

“…Findings of initial functional studies demonstrated that CAML overexpression in Jurkat T cells causes a rise in intracellular calcium, followed by NFAT transcription factor activation (1, 7). Later work linked CAML with the intracellular trafficking of diverse receptors and signaling proteins (17,18,21,22). Yet several properties of CAML do not fulfill the criteria expected for the putative HIV-1-tethering protein.…”

mentioning

confidence: 99%

Effect of Calcium-Modulating Cyclophilin Ligand on Human Immunodeficiency Virus Type 1 Particle Release and Cell Surface Expression of Tetherin

Bego

Dubé

Mercier

et al. 2009

J Virol

View full text Add to dashboard Cite

The human immunodeficiency virus type 1 (HIV-1) accessory protein Vpu enhances virus particle release by counteracting a host factor that retains virions at the surfaces of infected cells. It was recently demonstrated that cellular protein BST-2/CD317/Tetherin restricts HIV-1 release in a Vpu-dependent manner. Calciummodulating cyclophilin ligand (CAML) was also proposed to be involved in this process. We investigated whether CAML is involved in cell surface expression of Tetherin. Here, we show that CAML overexpression in permissive Cos-7 cells or CAML depletion in restrictive HeLa cells has no effect on HIV-1 release or on Tetherin surface expression, indicating that CAML is not required for Tetherin-mediated restriction of HIV-1 release.

show abstract

Calcium-modulating cyclophilin ligand regulates membrane trafficking of postsynaptic GABAA receptors

Cited by 37 publications

References 41 publications

Tail-anchored Protein Insertion in Mammals

Tail-anchored Protein Insertion in Mammals

CAML promotes prolactin-dependent proliferation of breast cancer cells by facilitating prolactin receptor signaling pathways

Effect of Calcium-Modulating Cyclophilin Ligand on Human Immunodeficiency Virus Type 1 Particle Release and Cell Surface Expression of Tetherin

Contact Info

Product

Resources

About