PUBLICATION
BNIP-H Recruits the Cholinergic Machinery to Neurite Terminals to Promote Acetylcholine Signaling and Neuritogenesis
- Authors
- Sun, J., Pan, C.Q., Chew, T.W., Liang, F., Burmeister, M., Low, B.C.
- ID
- ZDB-PUB-150908-8
- Date
- 2015
- Source
- Developmental Cell 34(5): 555-68 (Journal)
- Registered Authors
- Low, Boon Chaun
- Keywords
- none
- MeSH Terms
-
- Acetylcholine/metabolism*
- Animals
- Cell Line
- Choline O-Acetyltransferase/metabolism
- Cholinergic Agents/pharmacology
- Nerve Tissue Proteins/metabolism*
- Neurites/metabolism*
- Neurons/metabolism*
- Rats
- Signal Transduction*/physiology
- Synaptic Transmission/physiology
- PubMed
- 26343454 Full text @ Dev. Cell
Citation
Sun, J., Pan, C.Q., Chew, T.W., Liang, F., Burmeister, M., Low, B.C. (2015) BNIP-H Recruits the Cholinergic Machinery to Neurite Terminals to Promote Acetylcholine Signaling and Neuritogenesis. Developmental Cell. 34(5):555-68.
Abstract
Synthesis and release of neurotransmitters such as acetylcholine (ACh) are key to synaptic function. However, little is known about the spatial regulation of their synthesizing machinery. Here, we demonstrate that ataxia-related protein BNIP-H/Caytaxin links kinesin-1 (KLC1) to ATP citrate lyase (ACL), a key enzyme for ACh synthesis, and transports it toward neurite terminals. There, BNIP-H/ACL complex synergistically recruits another enzyme choline acetyltransferase (ChAT), leading to enhanced secretion of ACh. ACh then activates MAPK/ERK via muscarinic receptors to promote neurite outgrowth. In mice deficient in BNIP-H, ACL fails to interact with KLC1, and formation of the ACL/ChAT complex is prevented, whereas the disease-associated BNIP-H mutation fails to target ACL for neurite outgrowth. Significantly, Bnip-h knockdown in zebrafish causes developmental defect in motor neurons through impaired cholinergic pathway, leading to motor disorder. Therefore, precise targeting of the cholinergic machinery through BNIP-H is essential for the local production of ACh for morphogenesis and neurotransmission.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping