Krawczyk Pawel, Klopotowska Dagmara, Matuszyk Janusz
Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences, 12 R. Weigla Street, 53-114, Wroclaw, Poland.
Biochem Biophys Rep. 2024 Oct 23;40:101853. doi: 10.1016/j.bbrep.2024.101853. eCollection 2024 Dec.
TrkB and TrkC are quite common neurotrophin receptors found on the same cells in CNS. In the C-terminal tail, TrkB and TrkC differ only in two amino acid residues at positions immediately preceding the tyrosine residue, which, upon phosphorylation, becomes the docking site for phospholipase Cγ1 (PLCγ1). The question arose whether such a difference near the PLCγ1 docking site might contribute to differential response to neurotrophin. PC12 clones with the following receptors were obtained: wild-type TrkC, TrkC-Y820F with a defective PLCγ1 binding site, TrkC-T817S-I819V with two amino acid residues replaced with those in the TrkB tail. The outgrowth of neurite-like processes from TrkC-Y820F-containing cells appeared to be impaired, while the TrkC-T817S-I819V variant appeared more effective than wild-type TrkC in promoting the outgrowth of neurite-like processes after neurotrophin stimulation, at least in the compared PC12 cell clones. Taken together, both the tyrosine residue at the PLCγ1 docking site and the amino acid residues immediately preceding it appear important for TrkC-supported outgrowth of neurite-like processes.
TrkB和TrkC是中枢神经系统中同一细胞上常见的神经营养因子受体。在C末端尾巴区域，TrkB和TrkC仅在紧邻酪氨酸残基之前位置的两个氨基酸残基上存在差异，酪氨酸残基磷酸化后会成为磷脂酶Cγ1（PLCγ1）的停靠位点。于是产生了一个问题，即PLCγ1停靠位点附近的这种差异是否可能导致对神经营养因子的不同反应。获得了具有以下受体的PC12克隆：野生型TrkC、具有缺陷的PLCγ1结合位点的TrkC-Y820F、两个氨基酸残基被TrkB尾巴中的氨基酸残基取代的TrkC-T817S-I819V。含有TrkC-Y820F的细胞中神经突样突起的生长似乎受到损害，而在神经营养因子刺激后，TrkC-T817S-I819V变体在促进神经突样突起生长方面似乎比野生型TrkC更有效，至少在所比较的PC12细胞克隆中是这样。综上所述，PLCγ1停靠位点处的酪氨酸残基及其紧邻的氨基酸残基对于TrkC支持的神经突样突起生长似乎都很重要。
