Question

A calmodulin-regulated kinase (CaM-kinase) is involved in spatial learning and memory. This kinase is able to phosphorylate itself such that its kinase activity is now independent of the intracellular concentration of Ca2+. Thus, the kinase stays active after Ca2+ levels have dropped. Mice completely lacking this CaM-kinase have severe spatial learning defects but are otherwise normal.

a. Each of the following mutations also leads to similar learning defects. For each case explain why.
i. a mutation that prevents the kinase from binding ATP
ii. a mutation that deletes the calmodulin-binding part of the kinase
iii. a mutation that destroys the site of autophosphorylation

Answer 1

Mutations that prevent ATP binding, delete the calmodulin-binding part, or destroy the autophosphorylation site of the CaM-kinase would all result in similar learning defects.

Step-by-step explanation:

The calmodulin-regulated kinase (CaM-kinase) is involved in spatial learning and memory. It phosphorylates itself, allowing its kinase activity to remain independent of the intracellular calcium concentration. The mutations mentioned would all lead to similar learning defects:

1. Mutation preventing ATP binding: Without ATP, the kinase would not be able to phosphorylate itself and activate its kinase activity. This would result in the kinase being unable to function properly, leading to learning defects.
2. Mutation deleting the calmodulin-binding part: Calmodulin is needed for the kinase to be regulated by calcium. If the calmodulin-binding part is deleted, the kinase would not be able to bind to calmodulin and therefore would not be activated properly, resulting in learning defects.
3. Mutation destroying the autophosphorylation site: Autophosphorylation is necessary for the kinase to become active and independent of intracellular calcium concentration. If the autophosphorylation site is destroyed, the kinase would not be able to activate itself, leading to learning defects.