Figure 2: The role of α-tubulin glutamate post-translational modification is depicted here, and can be appreciated by the rapid Purkinje Cell neurodegeneration which occurs in pcd mice via functional loss of the deglutamylation enzyme, CCP1. At the top of the figure is the eleven carboxyl-terminal amino-acids of mouse α-tubulin. The terminal tyrosine reside, which is cleavable, is indicated in red. (A), to the left, detyrosination and polyglutamylation generate an α-tubulin isoform that can be acted upon by cytosolic carboxy-Peptidases, CCP1, CCP4, and CCP6. Each of these enzymes can cleave glutamate residues from the polyE side-chain down to the ‘branch point’, and cleave the second last gene-encoded glutamate, creating the Δ2-Tub isomer. The role of CCP5 alone is to specifically cleave the branch glutamate. (B), on the right side, addition of the branch point glutamate initiates this modification. Thereafter, the situation where CCP1 or Nna1 is absent (pink shading), hyperglutamylation – neurodegeneration; is contrasted with the normal CCP1 present situation (no shading), defined by equilibrated polyglutamylation. Redundant function of CCP4 and CCP6 does not compensate for CCP1 loss, as studies have shown CCP1 is the enzyme predominantly expressed in the neuron subset which undergoes degeneration in pcd mice. This illustration was modified from figure 7 and supplemental material 1st reported by Rogowski et al., (2010).