cDNAs were expressed in sec4-8 yeast cells, which 
contain a temperature-sensitive allele of SEC4, and 
were screened for suppression of the growth defect 
at the restrictive temperature of 37°C. Sec4 is a 
member of the Sec4/Yptl/rab branch of the Ras su- 
perfamily and is a protein involved in a late stage of 
the secretory pathway in yeast. A suppressing cDNA, 
MSS4, was isolated. MSS4 encodes a 1 4-kDa protein 
that appears to enhance the function of Sec4 by act- 
ing as a GDP-releasing protein. The Mss4 protein is 
similar in amino acid sequence to Dss4, a yeast pro- 
tein with similar biochemical properties. (This re- 
search was supported in part by a grant from the 
National Institutes of Health.) 
Autoimmunity to SV Proteins 
The GABA-synthesizing enzyme glutamic acid de- 
carboxylase (GAD) was found to be a major target of 
humoral autoimmunity in stiff-man syndrome (SMS) 
and in insulin-dependent diabetes mellitus (IDDM) . 
SMS is a rare and severe central nervous system dis- 
ease, while IDDM is a relatively common condition 
resulting from an autoimmune destruction of pan- 
creatic j8 cells. GAD is represented by two similar 
proteins, GAD65 and GAD67. GAD65 is associated 
with the cytoplasmic surface of SVs of GABAergic 
neurons and of SLMVs of pancreatic /3 cells. During 
the past year Dr. De Camilli and his colleagues have 
established that GAD65 is the dominant autoantigen 
in SMS and have started to identify regions of the 
molecule that are the primary target of humoral au- 
toimmunity. 
Additionally, a brain protein, the target of hu- 
moral autoimmunity in three cases of SMS negative 
for GAD autoantibodies, was characterized. This 
protein is concentrated in nerve terminals, raising 
the possibility that SMS may be associated with auto- 
immunity directed against nerve terminal proteins 
rather than against a specific SV protein. (This work 
was supported in part by a grant from the National 
Institutes of Health.) 
Dr. De Camilli is also Professor of Cell Biology 
at Yale University School of Medicine. 
Books and Chapters of Books 
Jahn, R., and De Camilli, P. 1991 . Membrane pro- 
teins of synaptic vesicles: markers for neurons and 
neuroendocrine cells, and tools for the study of 
neurosecretion. In Markers for Neural and En- 
docrine Cells: Molecular and Cell Biology, 
Diagnostic Applications (Gratzl, M., and Lang- 
ley, K., Eds ). Weinheim, FRG: VCH, pp 23-92. 
Articles 
Cameron, P.L., Siidhof, T.C., Jahn, R., and De Ca- 
milli, P. 1991- Colocalization of synaptophysin 
with transferrin receptors: implications for synap- 
tic vesicle biogenesis. / Cell Biol 11 5: 15 1-1 64. 
De Camilli, P. 1991. Co-secretion of multiple sig- 
nal molecules from endocrine cells via distinct 
exocytotic pathways. Trends Pharmacol Sci 
12:446-448. 
Mandell, J.W., Czernik, A.J., De Camilli, P., Green- 
gard. P., and Townes-Anderson, E. 1992. Differ- 
ential expression of synapsins I and II among rat 
retinal synapses. /A'^ew rose/ 12:1736-1749. 
Matteoli, M., Takei, K., Cameron, R., Hurlbut, P., 
Johnston, P. A., Siidhof, T.C., Jahn, R., and De 
Camilli, P. 1 99 1 ■ Association of rab3 with synap- 
tic vesicles at late stages of the secretory pathway. 
f Cell Biol 115:625-633. 
Matteoli, M., Takei, K., Perin, M.S., Siidhof, T.C., 
and De Camilli, P. 1992. Exo-endocytotic recy- 
cling of synaptic vesicles in developing processes 
of cultured hippocampal neurons. / Cell Biol 
117:849-861. 
Solimena, M., and De Camilli, P. 1991- Autoimmu- 
nity to glutamic acid decarboxylase (GAD) in 
Stiff-Man syndrome and insulin-dependent dia- 
betes mellitus. Trends Neurosci 14:452-457. 
Takei, K., Stukenbrok, H., Metcalf, A., Mignery, 
G.A., Siidhof, T.C., Volpe, P., and De Camilli, P. 
1992. Ca^^ stores in Purkinje neurons: endoplas- 
mic reticulum subcompartments demonstrated 
by the heterogeneous distribution of the InsP, re- 
ceptor, Ca^^-ATPase, and calsequestrin. / A^ewro- 
5a 12:489-505. 
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