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| ESSENTIAL FUNCTIONS OF SYNAPSIN-I AND SYNAPSIN-II IN SYNAPTIC VESICLE REGULATION |
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| Author(s): ROSAHL TW, SPILLANE D, MISSLER M, HERZ J, SELIG DK, WOLFF JR, HAMMER RE, MALENKA RC, SUDHOF TC |
| Source: NATURE Volume: 375 Issue: 6531 Pages: 488-493 Published: JUN 8 1995 |
| Times Cited: 392 References: 24 |
| Abstract: SYNAPTIC vesicles are coated by synapsins, phosphoproteins that account for 9% of the vesicle protein(1-3). To analyse the functions of these proteins, we have studied knockout mice lacking either synapsin I, synapsin II, or both. Mice lacking synapsins are viable and fertile with no gross anatomical abnormalities, but experience seizures with a frequency proportional to the number of mutant alleles. Synapsin-II and double knockouts, but not synapsin-I knockouts, exhibit decreased post-tetanic potentiation and severe synaptic depression upon repetitive stimulation. Intrinsic synaptic-vesicle membrane proteins, but not peripheral membrane proteins or other synaptic proteins, are slightly decreased in individual knockouts and more severely reduced in double knockouts, as is the number of synaptic vesicles. Thus synapsins are not required for neurite outgrowth, synaptogenesis or the basic mechanics of synaptic vesicle traffic, but are essential for accelerating this traffic during repetitive stimulation. The phenotype of the synapsin knockouts could be explained either by deficient recruitment of synaptic vesicles to the active zone, or by impaired maturation of vesicles at the active zone, both of which could lead to a secondary destabilization of synaptic vesicles. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV TEXAS, SW MED CTR, DEPT MOLEC GENET, DALLAS, TX 75235 USA
2. UNIV TEXAS, SW MED CTR, DEPT BIOCHEM, DALLAS, TX 75235 USA
3. UNIV TEXAS, SW MED CTR, HOWARD HUGHES MED INST, DALLAS, TX 75235 USA
4. UNIV CALIF SAN FRANCISCO, CTR NEUROBIOL & PSYCHIAT, DEPT PSYCHIAT, SAN FRANCISCO, CA 94143 USA
5. UNIV CALIF SAN FRANCISCO, CTR NEUROBIOL & PSYCHIAT, DEPT PHYSIOL, SAN FRANCISCO, CA 94143 USA
6. GOTHENBURG UNIV, ZENTRUM ANAT, D-37075 GOTTINGEN, GERMANY |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: RC188 |
| ISSN: 0028-0836 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |