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Localization of membrane proteins to the inner nuclear envelope
HEADLINES
Z Molecular zippers and meiotic checkpoints
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SYM, M., ENGEBRECHT,J. and ROEDER,G. S. (1993) ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis Cell 72, 365-378 An intriguing cytological feature of meiosis is the synaptonemal complex that intimately links homologous chromosomes following DNA replication. The close association of homologous chromosomes through this nucleoprotein complex is thought to promote recombination and successful chromosome segregation. However, the precise functions and molecular organization of the synaptonemal complex have remained obscure. Sym et al. report the cloning of the Saccharomyces cerevisiae ZIP1 gene whose protein product is required for successful sporulation and appears to be part of the synaptonemal complex. ZIP1 is expressed exclusively during meiosis and localizes along the entire length of synapsed pachytene chromosomes. In addition, ZIP1
has sequence homology to coiledcoil proteins and the number of heptad repeats in the coiled-coil region closely approximates to the width of the synaptonemal complex. Taken together, these data suggest a model whereby ZIP1 functions as a transverse filament in the synaptonemal complex, 'zippering up' aligned homologous chromosomes into a fully synapsed structure. In a zip1 null strain the duplicated chromosomes pair and associate at positions that may be sites of synaptic initiation and crossing over, but fail to join into intimately synapsed chromosome pairs. Despite the lack of a complete synaptonemal complex, meiotic recombination is initiated at almost wild-type frequency in zip1 mutants, but the recombination intermediates fail to be resolved before
the arrest conferred by the zip1 mutation. The mutant cells arrest uniformly in prophase I following the dissociation of homologous chromosome pairs, but before spindle formation. Segregation of the paired chromosomes is apparently not physically hindered; rather, no attempt at segregation seems to be made. Thus arrest may be conferred by a regulatory mechanism that responds to the accumulation of recombination intermediates or an improperly constructed synaptonemal complex. These observations reveal a novel meiotic checkpoint in yeast. Also, by demonstrating that chromosomes become committed to and initiate meiotic recombination without synapsis, Sym et aL fuel further speculation about the function of the synaptonemal complex.
Localization of membrane proteins to the inner nuclear envelope SOULLAM, B. and WORMAN, H. J. (1993) The amino-terminal domain of the lamin B receptor is a nuclear envelope targeting signal J. Cell Biol. 120, 1093-1100 How do proteins lodged in the inner nuclear envelope get there? Soullam and Worman have shed light on this question by analysing the targeting signal of the lamin B receptor (LBR), an inner nuclear envelope protein that comprises a nucleoplasmic Nterminal domain and eight putative transmembrane segments. They followed the localization of LBR, its Nterminal domain alone and chimeric LBR proteins in transfected COS cells by immunofluorescence microscopy. The N-terminal domain of LBR is transported into the nucleus after synthesis in the cytoplasm, and as part of a chimeric protein it is sufficient to target a type II integral membrane protein of the endoplasmic reticulum (ER), which is continuous with the outer nuclear envelope, to the inner nuclear envelope. Furthermore, replacement of the N-terminal domain of LBR with ~globin resulted in retention of most of the chimeric protein in the ER.
The authors suggest that the Nterminal domain of LBR, which presumably faces the cytoplasm when the protein is synthesized on the ER, serves to 'drag' the transmembrane segments of LBR across the pore membrane domain to the inner nuclear membrane. The mechanism underlying this movement is not known but the authors hint at two
TRENDS IN CELL BIOLOGYVOL. 3 MAY 1993
possibilities: the use of a nucleoplasmin-like bipartite motif in the N-terminal domain of LBP that may function as a nuclear localization signal in an active transport process, or diffusion of LBP within the nuclear membrane followed by trapping on the nuclear side as a result of binding of the N-terminal domain to nuclear components.
This month's headlineswere contributed by Catherine Brooksbank, Carolyn Elliss, David Stuartand Benjamin Glick. 1 49
Z Molecular zippers and meiotic checkpoints
<
uq
SYM, M., ENGEBRECHT,J. and ROEDER,G. S. (1993) ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis Cell 72, 365-378 An intriguing cytological feature of meiosis is the synaptonemal complex that intimately links homologous chromosomes following DNA replication. The close association of homologous chromosomes through this nucleoprotein complex is thought to promote recombination and successful chromosome segregation. However, the precise functions and molecular organization of the synaptonemal complex have remained obscure. Sym et al. report the cloning of the Saccharomyces cerevisiae ZIP1 gene whose protein product is required for successful sporulation and appears to be part of the synaptonemal complex. ZIP1 is expressed exclusively during meiosis and localizes along the entire length of synapsed pachytene chromosomes. In addition, ZIP1
has sequence homology to coiledcoil proteins and the number of heptad repeats in the coiled-coil region closely approximates to the width of the synaptonemal complex. Taken together, these data suggest a model whereby ZIP1 functions as a transverse filament in the synaptonemal complex, 'zippering up' aligned homologous chromosomes into a fully synapsed structure. In a zip1 null strain the duplicated chromosomes pair and associate at positions that may be sites of synaptic initiation and crossing over, but fail to join into intimately synapsed chromosome pairs. Despite the lack of a complete synaptonemal complex, meiotic recombination is initiated at almost wild-type frequency in zip1 mutants, but the recombination intermediates fail to be resolved before
the arrest conferred by the zip1 mutation. The mutant cells arrest uniformly in prophase I following the dissociation of homologous chromosome pairs, but before spindle formation. Segregation of the paired chromosomes is apparently not physically hindered; rather, no attempt at segregation seems to be made. Thus arrest may be conferred by a regulatory mechanism that responds to the accumulation of recombination intermediates or an improperly constructed synaptonemal complex. These observations reveal a novel meiotic checkpoint in yeast. Also, by demonstrating that chromosomes become committed to and initiate meiotic recombination without synapsis, Sym et aL fuel further speculation about the function of the synaptonemal complex.
Localization of membrane proteins to the inner nuclear envelope SOULLAM, B. and WORMAN, H. J. (1993) The amino-terminal domain of the lamin B receptor is a nuclear envelope targeting signal J. Cell Biol. 120, 1093-1100 How do proteins lodged in the inner nuclear envelope get there? Soullam and Worman have shed light on this question by analysing the targeting signal of the lamin B receptor (LBR), an inner nuclear envelope protein that comprises a nucleoplasmic Nterminal domain and eight putative transmembrane segments. They followed the localization of LBR, its Nterminal domain alone and chimeric LBR proteins in transfected COS cells by immunofluorescence microscopy. The N-terminal domain of LBR is transported into the nucleus after synthesis in the cytoplasm, and as part of a chimeric protein it is sufficient to target a type II integral membrane protein of the endoplasmic reticulum (ER), which is continuous with the outer nuclear envelope, to the inner nuclear envelope. Furthermore, replacement of the N-terminal domain of LBR with ~globin resulted in retention of most of the chimeric protein in the ER.
The authors suggest that the Nterminal domain of LBR, which presumably faces the cytoplasm when the protein is synthesized on the ER, serves to 'drag' the transmembrane segments of LBR across the pore membrane domain to the inner nuclear membrane. The mechanism underlying this movement is not known but the authors hint at two
TRENDS IN CELL BIOLOGYVOL. 3 MAY 1993
possibilities: the use of a nucleoplasmin-like bipartite motif in the N-terminal domain of LBP that may function as a nuclear localization signal in an active transport process, or diffusion of LBP within the nuclear membrane followed by trapping on the nuclear side as a result of binding of the N-terminal domain to nuclear components.
This month's headlineswere contributed by Catherine Brooksbank, Carolyn Elliss, David Stuartand Benjamin Glick. 1 49