PMID- 11099460 OWN - NLM STAT- MEDLINE DCOM- 20010208 LR - 20220309 IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 14 IP - 15 DP - 2000 Dec TI - Transport mechanisms in acetylcholine and monoamine storage. PG - 2423-34 AB - Sequence-related vesicular acetylcholine transporter (VAChT) and vesicular monoamine transporter (VMAT) transport neurotransmitter substrates into secretory vesicles. This review seeks to identify shared and differentiated aspects of the transport mechanisms. VAChT and VMAT exchange two protons per substrate molecule with very similar initial velocity kinetics and pH dependencies. However, vesicular gradients of ACh in vivo are much smaller than the driving force for uptake and vesicular gradients of monoamines, suggesting the existence of a regulatory mechanism in ACh storage not found in monoamine storage. The importance of microscopic rather than macroscopic kinetics in structure-function analysis is described. Transporter regions affecting binding or translocation of substrates, inhibitors, and protons have been found with photoaffinity labeling, chimeras, and single-site mutations. VAChT and VMAT exhibit partial structural and mechanistic homology with lactose permease, which belongs to the same sequence-defined superfamily, despite opposite directions of substrate transport. The vesicular transporters translocate the first proton using homologous aspartates in putative transmembrane domain X (ten), but they translocate the second proton using unknown residues that might not be conserved between them. Comparative analysis of the VAChT and VMAT transport mechanisms will aid understanding of regulation in neurotransmitter storage. FAU - Parsons, S M AU - Parsons SM AD - Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, USA. parsons@chem.ucsb.edu LA - eng GR - NS15047/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PT - Review PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Biogenic Monoamines) RN - 0 (Carrier Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Neuropeptides) RN - 0 (Vesicular Acetylcholine Transport Proteins) RN - 0 (Vesicular Biogenic Amine Transport Proteins) RN - 0 (Vesicular Monoamine Transport Proteins) RN - 0 (Vesicular Transport Proteins) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/*metabolism MH - Amino Acid Sequence MH - Biogenic Monoamines/*metabolism MH - Biological Transport MH - Carrier Proteins/antagonists & inhibitors/*metabolism MH - Membrane Glycoproteins/antagonists & inhibitors/*metabolism MH - *Membrane Transport Proteins MH - Models, Chemical MH - Molecular Sequence Data MH - *Neuropeptides MH - Thermodynamics MH - Vesicular Acetylcholine Transport Proteins MH - Vesicular Biogenic Amine Transport Proteins MH - Vesicular Monoamine Transport Proteins MH - *Vesicular Transport Proteins RF - 84 EDAT- 2000/12/02 11:00 MHDA- 2001/03/03 10:01 CRDT- 2000/12/02 11:00 PHST- 2000/12/02 11:00 [pubmed] PHST- 2001/03/03 10:01 [medline] PHST- 2000/12/02 11:00 [entrez] AID - 14/15/2423 [pii] AID - 10.1096/fj.00-0203rev [doi] PST - ppublish SO - FASEB J. 2000 Dec;14(15):2423-34. doi: 10.1096/fj.00-0203rev.