TABLE 1.
Summary of published CB1R mutants.
| Amino Acids | cDNA | Tag | Cell Type | Surface Expression | Trafficking Properties? | Signaling properties? | References | |
| Ct-tail truncation | 1–400 | human | – | (SCG) neurons and HEK293 cells |
Unaltered (in HEK293) |
– | Abolished G-protein coupling |
Nie and Lewis, 2001b |
| 1–417 | human | – | (SCG) neurons and HEK293 cells |
Unaltered (in HEK293) |
Enhanced constitutive internalization | ↓ G-protein activation | Nie and Lewis, 2001a, b | |
| ↑14 | rat | – | AtT20 | Unaltered | Prevented agonist induced internalization |
– | Hsieh et al., 1999 | |
| ↑14 | rat | – | HEK293 | Unaltered |
No effect on agonist induced internalization |
– | Hsieh et al., 1999 | |
| ↑14 | rat | Nt-GFP | rat hippocampal neurons |
Traffics to surface (axonal polarized) |
– | – | McDonald et al., 2007a, b | |
| ↑13 | rat | – | mouse hippocampal neurons (CB1R knockout) |
– | – | No desensitization | Straiker et al., 2012b | |
| Ct tail deletion | Δ418–439 | rat | – | Xenopus oocytes | – | Prevented β-arrestin-2/GRK mediated down-regulation |
No desensitization | Jin et al., 1999 |
| Δ419–460 | rat | – | mouse hippocampal neurons (CB1R-/-) |
– | – | No effect on desensitization | Straiker et al., 2012b | |
| ΔH9 (441–461) | rat | Nt-SBP-GFP | rat hippocampal neurons | Reduced in axons and dendrites | ↑ delivery to dendrites ↑ agonist-induced endocytosis |
↓ERK1/2 phosphorylation | Fletcher-Jones et al., 2019 | |
| Ct tail point mutation | L404F in H8 | human | – | HEK293 | Unaltered | ↑rate of internalisation | ↓ G-protein activation, ↓Ca2+ inhibition | Anavi-Goffer et al., 2007 |
| φ-A triple mutant in H8 (L404A/F408A/F412A) |
human | Ct-GFP | HEK293 | ER retention (localisation perturbed) |
– | ↓ ligand binding and ↓ G-protein activation | Ahn et al., 2010 | |
| S426A/S430A (phospho-null) |
rat | – | Xenopus oocytes and AtT20 cells |
Unaltered | Prevent β-arrestin-2/GRK mediated down-regulation | No desensitization | Jin et al., 1999 | |
| mutation of last 6 S/T-A (phospho-null) |
rat | – | HEK293 | Unaltered | Attenuates internalisation | – | Daigle et al., 2008b | |
| mutation of last 6 S/T-A (phospho-null) |
rat | – | mouse hippocampal neurons (CB-/-) |
– | – | No desensitization | Straiker et al., 2012b | |
| C415 | human | Ct-GFP | HEK293 and 5HSY-5Y |
Reduced surface localisation | ↑ diffusional mobility | ↓G protein coupling/activation (Gαi/o) | Oddi et al., 2012 | |
| D467A;T468A; S469A;A472G; L473A | rat | – | HEK293 | No CRIP1a-dependent reduction in internalization | – | Mascia et al., 2017 | ||
| Nt | Nt truncations (↑64,↑80,↑89,ssNt) |
human | Nt-myc | HEK293 | ↑ surface localisation | Facilitates ER exit | – | Andersson et al., 2003 |
| TM domains | 2nd TM domain (D164N) |
rat | – | AtT20 | Unaltered | No internalization | KIR current potential inhibited | Roche et al., 1999 |
| 2nd TM domain (D164N) |
rat | – | (SCG) neurons | Unaltered | No constitutive internalization | – | Nie and Lewis, 2001b | |
| 2nd TM domain (D164N) |
rat | Nt-GFP | rat hippocampal neurons | Traffics to surface (axonal polarized) |
– | – | McDonald et al., 2007b | |
| 3rd TM domain (T210A/I) |
rat | Ct-GFP | HEK293 | ↑/↓surface localisation (T210A/I) ↓surface localisation (T210I) |
↓ constitutive internalization (T210A) ↑ constitutive internalization (T210I) |
T210I: hyperactive T210A: hypoactive |
D’Antona et al., 2006 | |
| 3rd TM domain (T210A/I) |
rat | Nt-FLAG, Ct-GFP | rat hippocampal neurons | Non-polarized (T210A) ↓surface localisation (T210I) |
↑ constitutive internalization (T210I) | T210I: hyperactive T210A: hypoactive |
Simon et al., 2013 | |
| 4th TM domain F238L | rat | Nt-HA | HEK293; Rat hippocampal neurons |
↑lipid raft association ↓surface localisation ↑axonal polarity |
↑ lipid raft-mediated constitutive internalization | – | Wickert et al., 2018 | |
| EC loop | 2nd EC Loop (TM4-TM5) |
human | Ct-GFP | HEK293 | ↓ surface expression | ER retention (W255A, N256A, F268A) |
ligand binding perturbed | Ahn et al., 2009b |