Regulation of axonal growth and neuromuscular junction formation by neuronal phosphatase and tensin homologue signaling
| Autor: | Pan P. Li, H. Benjamin Peng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Embryo
Nonmammalian Xenopus Synaptogenesis Neuromuscular Junction Down-Regulation Xenopus Proteins Neuromuscular junction Postsynaptic potential medicine Organometallic Compounds Tensin Myocyte PTEN Animals Molecular Biology Acetylcholine receptor biology Muscles PTEN Phosphohydrolase Cell Biology Articles Signaling Axons Cell biology medicine.anatomical_structure Biochemistry nervous system biology.protein medicine.symptom Muscle contraction Phenanthrolines Signal Transduction |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Axonal growth and synaptogenesis are sequential events of neuronal development. Phosphatase and tensin homologue (PTEN) is expressed in motor neurons, and its disruption leads to continued axonal extension, even upon muscle contact, leading to synaptogenic suppression. Thus PTEN is involved in target-mediated cessation of axonal growth and subsequent synaptic differentiation. During the development of the vertebrate neuromuscular junction (NMJ), motor axon tips stop growing after contacting muscle and transform into presynaptic terminals that secrete the neurotransmitter acetylcholine and activate postsynaptic ACh receptors (AChRs) to trigger muscle contraction. The neuron-intrinsic signaling that retards axonal growth to facilitate stable nerve–muscle interaction and synaptogenesis is poorly understood. In this paper, we report a novel function of presynaptic signaling by phosphatase and tensin homologue (PTEN) in mediating a growth-to-synaptogenesis transition in neurons. In Xenopus nerve–muscle cocultures, axonal growth speed was halved after contact with muscle, when compared with before contact, but when cultures were exposed to the PTEN blocker bisperoxo (1,10-phenanthroline) oxovanadate, axons touching muscle grew ∼50% faster than their counterparts in control cultures. Suppression of neuronal PTEN expression using morpholinos or the forced expression of catalytically inactive PTEN in neurons also resulted in faster than normal axonal advance after contact with muscle cells. Significantly, interference with PTEN by each of these methods also led to reduced AChR clustering at innervation sites in muscle, indicating that disruption of neuronal PTEN signaling inhibited NMJ assembly. We thus propose that PTEN-dependent slowing of axonal growth enables the establishment of stable nerve–muscle contacts that develop into NMJs. |
| Databáze: | OpenAIRE |
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