Table 1.
Summary of CRMP2 post-translational modifications and functional consequences.
| Enzyme | Function | Effect of loss of function mutations | Diseases | Targeting peptides and compounds | Reference(s) | |
|---|---|---|---|---|---|---|
| Y32 (phosphorylation) | Fyn, Fes/Fps | Inhibition of Neurite outgrowth, Decreased CRMP2 SUMOylation and NaV1.7 membrane localization | Promotes Neurite outgrowth, Protects NaV1.7 from endocytosis | Decreased at pre- synaptic sites in neuropathic pain | Unknown | [91,95,46,13] |
| Y479 (phosphorylation) | Yes, Fer, Fyn, Fes/Fps | Cytoskeletal reorganization in T-cell migration, loss of affinity for microtubules, disruption of CRMP2 tetramers | Reduced cell polarization and motility | HTLV infections | Unknown | [94,189] |
| Y499 (phosphorylation) | Fer | loss of affinity for microtubules, disruption of CRMP2 tetramers | Unknown | Ovarian cancer | Unknown | [92] |
| T509/T514/S518 (phosphorylation) | GSK3β | loss of affinity for tubulin, cellular proliferation, disruption of CRMP2 tetramers | Unknown | AD, neuropathic pain, bipolar disorder | Naringenin, (S)- lacosamide, lanthionine ketimine ester, edonerpic maleate, | [27,46,89,90,109,137,22,82,67,188] |
| S522 (phosphorylation) | Cdk5 | loss of affinity for tubulin, cancer cell proliferation, promotes CaV2.2 and NaV1.7 membrane localization, disruption of CRMP2 tetramers | Promotes neurite outgrowth, decreases CaV2.2 And NaV1.7 trafficking | AD, neuropathic pain, NF1, bipolar disorder, cancer | (S)- lacosamide, lanthionine ketimine ester, edonerpic maleate | [131–133,9,134,27,46,89,90,166,11,165,10,169,22,180,181,23,182,82,67,188] |
| T555 (phosphorylation) | RhoK, CaM KII | Decreased affinity for tubulin, decreased neurite outgrowth | Promotes neurite outgrowth, decreased Ca2+ influx | AD, MS | Unknown | [19,110,105,111,112] |
| K374 (SUMOylation) | Ubc9 | NaV1.7 trafficking | Decreases NaV1.7 surface expression | neuropathic pain | CRMP2 SUMOylation motif peptide | [12,13,44,161,124,47,45,46,160] |
| S517 (O- GlcNAcylation) | Unknown | Unknown | Unknown | Unknown | Unknown | [52,53] |
| C504 (oxidation) | Unknown | CRMP2 dimerization, microtubule regulation, growth cone collapse | Unknown | Unknown | Unknown | [117,116,118] |