scholarly journals The adaptor protein GULP promotes Jedi-1–mediated phagocytosis through a clathrin-dependent mechanism

2014 ◽  
Vol 25 (12) ◽  
pp. 1925-1936 ◽  
Author(s):  
Chelsea S. Sullivan ◽  
Jami L. Scheib ◽  
Zhong Ma ◽  
Rajan P. Dang ◽  
Johanna M. Schafer ◽  
...  

During the development of the peripheral nervous system, the large number of apoptotic neurons generated are phagocytosed by glial precursor cells. This clearance is mediated, in part, through the mammalian engulfment receptor Jedi-1. However, the mechanisms by which Jedi-1 mediates phagocytosis are poorly understood. Here we demonstrate that Jedi-1 associates with GULP, the mammalian homologue of CED-6, an adaptor protein required for phagocytosis mediated by the nematode engulfment receptor CED-1. Silencing GULP or mutating the NPXY motif in Jedi-1, which is required for GULP binding, prevents Jedi-1–mediated phagocytosis. How GULP promotes engulfment is not known. Of interest, we find that Jedi-1–induced phagocytosis requires GULP binding to clathrin heavy chain (CHC). During engulfment, CHC is tyrosine phosphorylated, which is required for Jedi-mediated engulfment. Both phosphoclathrin and actin accumulate around engulfed microspheres. Furthermore, knockdown of CHC in HeLa cells prevents Jedi-1–mediated engulfment of microspheres, and knockdown in glial precursors prevents the engulfment of apoptotic neurons. Taken together, these results reveal that Jedi-1 signals through recruitment of GULP, which promotes phagocytosis through a noncanonical phosphoclathrin-dependent mechanism.

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3735-3743 ◽  
Author(s):  
V. Van De Bor ◽  
R. Walther ◽  
A. Giangrande

In flies, the choice between neuronal and glial fates depends on the asymmetric division of multipotent precursors, the neuroglioblast of the central nervous system and the IIb precursor of the sensory organ lineage. In the central nervous system, the choice between the two fates requires asymmetric distribution of the glial cell deficient/glial cell missing (glide/gcm) RNA in the neuroglioblast. Preferential accumulation of the transcript in one of the daughter cells results in the activation of the glial fate in that cell, which becomes a glial precursor. Here we show that glide/gcm is necessary to induce glial differentiation in the peripheral nervous system. We also present evidence that glide/gcm RNA is not necessary to induce the fate choice in the peripheral multipotent precursor. Indeed, glide/gcm RNA and protein are first detected in one daughter of IIb but not in IIb itself. Thus, glide/gcm is required in both central and peripheral glial cells, but its regulation is context dependent. Strikingly, we have found that only subsets of sensory organs are gliogenic and express glide/gcm. The ability to produce glial cells depends on fixed, lineage related, cues and not on stochastic decisions. Finally, we show that after glide/gcm expression has ceased, the IIb daughter migrates and divides symmetrically to produce several mature glial cells. Thus, the glide/gcm-expressing cell, also called the fifth cell of the sensory organ, is indeed a glial precursor. This is the first reported case of symmetric division in the sensory organ lineage. These data indicate that the organization of the fly peripheral nervous system is more complex than previously thought.


Stem Cells ◽  
2007 ◽  
Vol 25 (2) ◽  
pp. 340-353 ◽  
Author(s):  
Cecile Dromard ◽  
Sylvain Bartolami ◽  
Loïc Deleyrolle ◽  
Hirohide Takebayashi ◽  
Chantal Ripoll ◽  
...  

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3549-3560 ◽  
Author(s):  
J.F. Emery ◽  
E. Bier

The Drosophila pan-neural genes deadpan (dpn) and scratch (scrt) are expressed in most or all developing neural precursor cells of the central nervous system (CNS) and peripheral nervous system (PNS). We have identified a cis-acting enhancer element driving full pan-neural expression of the dpn gene which is composed of independent CNS- and PNS-specific subelements. We have also identified CNS- and PNS-specific subelements of the scrt enhancer. Deletion analysis of the dpn and scrt PNS-specific subelements reveals that PNS specificity of these two evolutionarily unrelated enhancers is achieved in part by repression of CNS expression. We discuss the implications of the striking organizational similarities of the dpn, scrt, and sna pan-neural enhancers.


Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 131-139 ◽  
Author(s):  
S. Vincent ◽  
J.L. Vonesch ◽  
A. Giangrande

Glial cells constitute the second component of the nervous system and are important during neuronal development. In this paper we describe a gene, glial cell deficient, (glide), that is necessary for glial cell fate commitment in Drosophila melanogaster. Mutations at the glide locus prevent glial cell determination in the embryonic central and peripheral nervous system. Moreover, we show that the absence of glial cells is the consequence of a cell fate switch from glia to neurones. This suggests the existence of a multipotent precursor cells in the nervous system. glide mutants also display defects in axonal navigation, which confirms and extends previous results indicating a role for glial cells in these processes.


Development ◽  
1992 ◽  
Vol 115 (2) ◽  
pp. 519-526
Author(s):  
C. Rudel ◽  
H. Rohrer

To identify and analyse precursor cells of neuronal and glial cell lineages during the early development of the chick peripheral nervous system, monoclonal antibodies were raised against a population of undifferentiated cells of E6 dorsal root ganglia (DRG). Non-neuronal cells of E6 DRG express surface antigens that are recognized by four monoclonal antibodies, G1, G2, GLI 1 and GLI 2. The proportion of non-neuronal cells in DRG that express the GLI 1 antigen is very high during ganglion formation (80% at E4) and decreases during later development (15% at E14). GLI 2 antigen is expressed only on a minority of the cells at E6 and increases with development. The G1 and G2 antigens are expressed on about 60–80% of the cells between E6 and E14. All cells that express the established glia marker O4 are also positive for the new antigens. In addition, it was demonstrated that GLI 1-positive cells from early DRG, which are devoid of O4 antigen, could be induced in vitro to express the O4 antigen. Thus, the antigen-positive cells are considered as glial cells or glial precursor cells. Surprisingly, the antigen expression by satellite cells of peripheral ganglia is dependent on the type of ganglion: antigens G1, G2 and GLI 1 were not detectable on glial cells of lumbosacral sympathetic ganglia and GLI 2 was expressed only by a small subpopulation. These results demonstrate an early immunological difference between satellite cells of sensory DRG and sympathetic ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)


Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2923-2936 ◽  
Author(s):  
R. Brewster ◽  
R. Bodmer

The peripheral nervous system (PNS) of Drosophila is a preferred model for studying the genetic basis of neurogenesis because its simple and stereotyped pattern makes it ideal for mutant analysis. Type I sensory organs, the external (bristle-type) sensory organs (es) and the internal (stretch-receptive) chordotonal organs (ch), have been postulated to derive from individual ectodermal precursor cells that undergo a stereotyped pattern of cell division. Little is known about the origin and specification of type II sensory neurons, the multiple dendritic (md) neurons. Using the flp/FRT recombinase system from yeast, we have determined that a subset of md neurons derives from es organ lineages, another subset derives from ch organ lineages and a third subset is unrelated to sensory organs. We also provide evidence that the genes, numb and cut, are both required for the proper differentiation of md neurons.


Author(s):  
S.S. Spicer ◽  
B.A. Schulte

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.


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