Nerve growth factor receptors on PC12 cells: ligand-induced conversion from low- to high-affinity states

The pheochromocytoma PC12 cell possesses specific cell surface receptors that bind nerve growth factor (NGF) with two different affinities. The rate of dissociation of NGF from the higher affinity receptor is slower than from the lower affinity receptor; this rate is reduced to essentially zero at low temperature, allowing the extent of high-affinity binding to be determined. When NGF is added to PC12 cells, only low-affinity binding is observed. After a short lag period, high-affinity binding also appears and increases slowly. If NGF is removed from the medium after binding is initiated, high-affinity receptors continue to be formed at the expense of low-affinity receptors. The increase in receptor affinity is accompanied by a transfer of the NGF-receptor complex from a trypsin-sensitive to a trypsin-resistant state. This transfer does not involve internalization of the NGF. The data show that NGF binds first to receptors of low affinity and that the binding induces a conversion of a proportion of the receptors to a higher affinity state. It is also consistent with a model in which the change in affinity is due either to conformational changes in the receptor or to interaction of the occupied receptor with other receptors or with effector proteins in cell plasma membrane.