BMP signaling modulates the probability of neurotransmitter release and readily releasable pools in Drosophila neuromuscular junction synapses

Abstract

The structure and function of synapses is modulated by the interaction of presynaptic and postsynaptic neurons via cell adhesion molecules or secreted signal molecules. Bone morphogenic protein (BMP) is a secreted molecule mediating retrograde signaling that is involved in the formation and maintenance of synaptic structure throughout many animal species. However, how BMP signaling modulates presynaptic neurotransmitter release is not yet clear. We studied the function of BMP signaling factors in neurotransmitter release in Drosophila neuromuscular synapses using loss-of-function mutants in genes for BMP modulators, Wit, Mad, and Dad. Larvae with mutations in wit and mad commonly showed a decreased synaptic bouton number in neuromuscular synapses. Larvae with dad mutations showed an increased bouton number. The amplitudes of miniature EJC (mEJC) were normal for these mutants. Wit and mad mutants showed decreased evoked EJC (eEJC) amplitude and increased paired pulse facilitation, implying impaired presynaptic neurotransmitter release. We found a reduction in readily releasable neurotransmitters pool sizes in wit and mad mutants. However, dad mutants showed a normal probability of neurotransmitter release and readily releasable pool sizes and normal eEJC amplitude even with clear abnormalities in synaptic structure. These results suggested that BMP signaling was critical for each step of presynaptic neurotransmission. The results also suggested that BMP signaling modulated both synaptic structure and function independently and specifically.

Keywords: Bone morphogenic protein; Drosophila; Neuromuscular junction; Neurotransmitter release; Release probability; Synaptic vesicle pool.