Human 5-HT3A -- Ala 478

Species Original Mutated to Mutation
Human Ala 478

Gly

Val

Leu

A478G

A478V

A478L

Rat Equivalent Ala 477    
Mouse Equivalent Ala 483    

 

Ala478Gly, Ala478Val, Ala478Leu

A478G and A478V mutations, in the human 5-HT3A subunit, had little effect on [3H] granisetron binding, relative to the WT 5-HT3AR, when receptors were expressed in COS cells. By comparison the A478L mutation resulted in a large reduction in [3H] granisetron binding.

The A478L mutant also resulted in a decrease in surface labeling, relative to the WT 5-HT3AR.

Removal of residue 478 resulted in a reduction in [3H] granisetron binding.

 

Tyr477Ala

The Y477A mutation in the human 5-HT3A subunit, exhibited increased [3H]granisetron binding relative to WT 5-HT3AR, when receptors were expressed in COS cells.

The 5-HT3A Y477A mutant also exhibited increased surface labeling relative to WT 5-HT3AR.

In addition, when the Tyr at position 477 (in mutant Q476A) was mutated to Ala, the result was an increase in surface expression, relative to the WT 5-HT3AR.

Removal of residue 477 and 478 (from the WT 5-HT3AR) resulted in a decrease in [3H] granisetron binding and surface labeling (see Table).

 

Gln476Ala

The Q476A mutation in the human 5-HT3A subunit exhibited increased [3H] granisetron binding relative to WT-5-HT3A, when receptors were expressed in COS cells.

The 5-HT3A Q476A mutant also exhibited increased surface labeling relative to WT 5-HT3AR.

In addition, when the Glu at position 476 (in mutant Y477A) was mutated to Ala, the result was an increase in surface expression, relative to the WT 5-HT3AR.

Removal of residues 476,477 and 478 (in the WT 5-HT3AR) resulted in a decrease in [3H] granisetron binding and surface labeling (see Table).




Name Mutations Truncations Relative(to WT-3A) Radioligand Binding Relative (to WT-3A) Membrane Expression
h-5HT-3A Q-Y-A      
N-4TM-QYG
Q-Y-G
  - NC
N-4TM-QYV
Q-Y-V
  - NC
N-4TM-QYL
Q-Y-L
  --- --
         
N-4TM-AYA
A-Y-A
  ++++ ++
N-4TM-QAA
Q-A-A
  ++++ ++
         
N-4TM-AAA
A-A-A
  +++ ++
N-4TM-AA
A-A-X
  -- ---
N-4TM-A
A-X-X
  ---- ----
         
N-4TM
 
X-X-X
---- ---
N-4TM-Q
 
Q-X-X
---- --
N-4TM-QY
 
Q-Y-X
---- --
         
Slight Reduction
-
Slight Increase
+
NC= No change
Reduction
--
Increase
++  
Large Reduction
---
Large Increase
+++  
Very Large reduction
----
Very Large Increase
++++  

 

Butler AS , Lindesay SA , Dover TJ , Kennedy MD , Patchell VB , Levine BA , Hope AG , Barnes NM (2009). Importance of the C-terminus of the human 5-HT3A receptor subunit.Neuropharmacology.56(1):292-302.

 

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