TRP channel–associated factors are a novel protein family that regulates TRPM8 trafficking and activity
Résumé
TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor-activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named "TRP channel-associated factors" (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity.
Mots clés
Abbreviations used in this paper: EAPA2
Experimental Autoimmune Prostatitis Antigen 2
FRET
Förster resonance energy transfer
HEK
human embryonic kidney
LNCaP
lymph node carcinoma of prostate
ML
maximum likelihood method
qPCR
quantitative real-time PCR
TCAF
TRP channel-associated factor
TCSPC
time-correlated single photon counting
TD FLIM
time-domain fluorescence lifetime imaging microscopy
TRP
transient receptor potential
Domaines
Génétique des populations [q-bio.PE]
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TRP_channel-associated_factors_are_a_novel_protein_family_that_regulates.pdf (4.26 Mo)
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| Origine | Publication financée par une institution |
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