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Students of cell biology could be excused for thinking that laminin biology evolved purely to vex them. Multiple different laminins〞combinations of , ?, and subunits that make up at least 15 different versions of this heterotrimeric protein〞are expressed in different places at different times, making a sensible analysis of this protein family a challenge. Most researchers have started with knockout experiments, but it is hardly surprising when a knockout defect correlates with the time and place of normal expression. Perhaps any laminin would suffice in the deleted laminin's place.
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Now, Kikkawa et al. (page 187) find that this is not the case. They uncover a specialized function for the laminin 5 isoform (not to be confused with laminin-5) during development of the kidney glomerular basement membrane (GBM).6 A u3 a: C& T. l
7 H0 g7 l4 ^6 i# B/ nLaminins are key ingredients of basement membranes, which are both structural barriers and platforms for cellular interaction. GBM laminins present at the early, S-shape stage of kidney development contain the 1 subunit, but are replaced at the later capillary loop stage with ones that contain 5. When the researchers made mice lacking the laminin 5 chain (Lama5-/-) a few years ago, the mice died with a plethora of developmental glitches, including severe kidney defects. So the 1– 5 switch is critical for kidney development.
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They have now studied this further using MR51〞a chimeric laminin chain that is mostly 5 but has the laminin G domains of 1. (G domains are specific to laminin chains.) MR51 nicely rescues the GBM defect of the Lama5-/- mutant, but capillary loops still are not made. A similar phenotype is seen in mice that lack mesangial cells, as these cells supply tension to maintain capillary loop structure. Although mesangial cells were present in the MR51, Lama5-/- mice, they could not stick to the GBM.
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8 m$ i) Y/ R& [' u$ h: ?( {5 B. lTwo proteins on mesangial cells, an integrin and the Lutheran blood group glycoprotein, were needed to grab onto the G domains of laminin 5. Thus, the laminin 5 isoform has both a general role in GBM integrity and a specialized role that allows mesangial cells to hold onto the GBM.(Mesangial cells (mc) need to bind to a s) |
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发表于 2009-3-6 00:36
发表于 2015-6-1 20:24
