THY-1, THE ENIGMATIC EXTROVERT ON THE NEURONAL SURFACE

被引:45
作者
MORRIS, R
机构
[1] Laboratory of Neurobiology, National Institute for Medical Research, London, NW7 1AA, Mill Hill
关键词
D O I
10.1002/bies.950141014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thy-1 is a small glycoprotein of 110 amino acids which, folded in the characteristic structure of an immunoglobulin variable domain(1), are anchored to the plasma membrane via a glycophosphatidylinositol (GPI) tail(2,3) (Fig. 1). It is a major component of the surface of various cell types, including neurons, at certain stages of their development(4). These qualities doubtlessly appeal to certain cognoscenti, but it is not clear why they would raise Thy-1 to the status of a favourite molecule. Indeed, few scientists readily admit to having a favourite. We study individual molecules because science is rooted in specific observations; but we do so in order to discover mechanisms of general importance. A molecule's appeal is dependent on its ability to reveal novel aspects of how nature works. Thy-1 has been unusual in this respect. It was the first lymphocyte surface antigen shown to be restricted to a functional subset of lymphocytes (T cells in the mouse), a finding crucial to the development of cellular immunology(5); it was one of the first cell surface molecules to be sequenced and indicated the importance of immunoglobulin domains and GPI anchors as structural motifs(1-3); it has been pivotal in studies demonstrating that GPI-anchored molecules are able to signal across the membrane they do not span(6,7). Thy-1 has revealed this much, however, with the charm of an adroit stripper: it has always promised glimpses of things more exciting than that displayed. In particular, the function of this molecule has never emerged. Our current work on Thy-1 in the nervous system is, we believe, finally prizing this last secret into the open. It suggests that Thy-1 on the neuronal surface interacts with one of the main glial types of adult brain, the astrocyte, to restrict axonal growth(8). There is no current consensus that astrocytes do regulate such growth, and this is the wider question we are addressing from the perspective of Thy-1. At issue also is how to progress from knowing the nature of a molecule to defining its function. This task has already been achieved with molecules which were harder to characterise than Thy-1. The problem is a classic Catch 22 situation: Thy-1 has been readily characterised because it is small and abundant (it is ten times more abundant than any other surface glycoprotein on rat thymocytes(9)); but since there is so much of it, whatever it does it must do rather badly (or there would be no need to have so much of it!). Defining a function based on low activity or affinity is not trivial.
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页码:715 / 722
页数:8
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共 33 条
[1]   ESTIMATION OF AMOUNT AND TISSUE DISTRIBUTION OF RAT THY-1.1 ANTIGEN [J].
ACTON, RT ;
MORRIS, RJ ;
WILLIAMS, AF .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1974, 4 (09) :598-602
[2]  
BARBONI E, 1991, IMMUNOLOGY, V72, P457
[3]   EXTENSIVE ELONGATION OF AXONS FROM RAT-BRAIN INTO PERIPHERAL-NERVE GRAFTS [J].
BENFEY, M ;
AGUAYO, AJ .
NATURE, 1982, 296 (5853) :150-152
[4]   SOME ASPECTS OF NORMAL AND ABNORMAL CELL SURFACE GENETICS [J].
BOYSE, EA ;
OLD, LJ .
ANNUAL REVIEW OF GENETICS, 1969, 3 :269-&
[5]   POLARIZED SORTING OF GLYPIATED PROTEINS IN HIPPOCAMPAL-NEURONS [J].
DOTTI, CG ;
PARTON, RG ;
SIMONS, K .
NATURE, 1991, 349 (6305) :158-160
[6]   OCCURRENCE OF A THETA-LIKE ANTIGEN IN RATS [J].
DOUGLAS, TC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1972, 136 (05) :1054-&
[7]  
FAIVRESARRAILH C, 1992, J NEUROSCI, V12, P257
[8]  
FERGUSON MAJ, 1988, ANNU REV BIOCHEM, V57, P285
[9]   INTRACELLULAR-TRANSPORT IN NEURONS [J].
GRAFSTEIN, B ;
FORMAN, DS .
PHYSIOLOGICAL REVIEWS, 1980, 60 (04) :1167-1283
[10]  
Graziadei PPC, 1978, NEURONAL PLASTICITY, P131