Abstract
Pancreatic beta cells and neuronal cells show a large number of similarities. For example, functional receptors for nerve growth factor are present in beta cells. Here we investigate whether TrkC, a neuronal high affinity receptor for neurotrophin-3, is expressed in the insulin-secreting cell line INS-1. We demonstrate the expression in INS-1 cells of mRNAs coding for TrkC identical in size to those found in the brain. As in neuronal cells, different alternatively spliced forms of TrkC mRNA, differing by the insertion of an alternative exon in their kinase domain, were expressed in INS-1 cells. TrkC protein is also expressed in INS-1 cells and is functional. Indeed, when INS-1 cells were treated with neurotrophin-3, TrkC became phosphorylated on tyrosine residues, and the expression of early response genes was induced. This activation of the receptor was paralleled by a rapid and transient increase in cytosolic free calcium due to an influx of extracellular calcium. Functional receptors for NT-3 are thus expressed in INS-1 cells. This cell line provides a new model for the study of NT-3 signal transduction and should be useful in the understanding of the role of neurotrophins in insulin-secreting cells.
Highlights
The insulin-secreting beta cells of the pancreas are similar in many ways to neuronal cells [1,2,3]
We report that the insulin-secreting cell line INS-1 expresses functional receptors to NT-3
By Northern blot analysis and RT-PCR, mRNAs coding for TrkC, a high affinity NT-3 receptor, are detected in INS-1 cells, identical in size to those found in the brain
Summary
The insulin-secreting beta cells of the pancreas are similar in many ways to neuronal cells [1,2,3]. The family of neurotrophic factors contains NGF, the first neurotrophin to be identified [7], and brain-derived neurotrophic factor (BDNF) [8] and neurotrophin-3 (NT-3) [9, 10] Signal transduction by these neurotrophins is initiated by high affinity binding to and activation of specific tyrosine kinase receptors. Whereas the expression of NGF and BDNF has been detected only in a limited number of peripheral tissues, NT-3 mRNAs have been detected in all the tissues tested, including brain, heart, skin, gut, muscle, lung, spleen, and liver [9, 10] This ubiquitous pattern of expression suggests that NT-3 could act outside the nervous system. It has been shown recently that melanocytes constitutively express low levels of TrkC and that NT-3 prevents cell death of melanocytes [19]
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