Saxena Smita, Howe Charles L, Cosgaya José M, Hu Minjie, Weis Joachim, Krüttgen Alex
Division of Neuropathology, Institute of Pathology, University of Bern, CH-3010 Bern, Switzerland.
Mol Cell Neurosci. 2004 Jun;26(2):292-307. doi: 10.1016/j.mcn.2004.02.006.
Neurotrophins transmit signals retrogradely from synapses to cell bodies by two different types of surface receptors, p75NTR and Trks. Compared to TrkA, the function of p75NTR in nerve growth factor (NGF) endocytosis is less clear, and it is unknown whether p75NTR by itself may internalize other neurotrophins besides NGF. We directly compared TrkA and p75NTR for their ability to internalize NGF, and we also examined the endocytosis of iodinated brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) by p75NTR. Cells expressing solely TrkA internalized NGF more efficiently than cells expressing p75NTR. Surprisingly, cells expressing only p75NTR internalized far more BDNF or NT3 than NGF. Moreover, p75NTR was more important for surface binding than for intracellular accumulation of each neurotrophin. Finally, we established a mechanistic role for the clathrin pathway in p75NTR endocytosis. Our results suggest that p75NTR may have multiple roles in different subcellular locations, functioning both at the cell surface and also within endocytic compartments.
神经营养因子通过两种不同类型的表面受体——p75神经营养因子受体（p75NTR）和酪氨酸激酶受体（Trks），从突触向细胞体逆向传递信号。与TrkA相比，p75NTR在神经生长因子（NGF）内吞作用中的功能尚不清楚，而且除了NGF之外，p75NTR自身是否能够内化其他神经营养因子也不清楚。我们直接比较了TrkA和p75NTR内化NGF的能力，并且还检测了p75NTR对碘化脑源性神经营养因子（BDNF）和神经营养因子-3（NT3）的内吞作用。仅表达TrkA的细胞比表达p75NTR的细胞更有效地内化NGF。令人惊讶的是，仅表达p75NTR的细胞内化的BDNF或NT3远比NGF多。此外，p75NTR对每种神经营养因子的表面结合比对细胞内积累更为重要。最后，我们确定了网格蛋白途径在p75NTR内吞作用中的机制作用。我们的结果表明，p75NTR可能在不同的亚细胞位置具有多种作用，在细胞表面以及内吞小室中均发挥功能。
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