Biomedical Engineering Graduate Program, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Traffic. 2009 May;10(5):600-14. doi: 10.1111/j.1600-0854.2009.00887.x. Epub 2009 Jan 24.
Lysosomes play a central role in the degradation of proteins and other macromolecules. The mechanisms by which receptors are transferred to lysosomes for constitutive degradation are poorly understood. We have analyzed the processes that lead to the lysosomal delivery of the Fc receptor, FcRn. These studies provide support for a novel pathway for receptor delivery. Specifically, unlike other receptors that enter intraluminal vesicles in late endosomes, FcRn is transferred from the limiting membrane of such endosomes to lysosomes, and is rapidly internalized into the lysosomal lumen. By contrast, LAMP-1 persists on the limiting membrane. Receptor transfer is mediated by tubular extensions from late endosomes to lysosomes, or by interactions of the two participating organelles in kiss-and-linger-like processes, whereas full fusion is rarely observed. The persistence of FcRn on the late endosomal limiting membrane, together with selective transfer to lysosomes, allows this receptor to undergo recycling or degradation. Consequently, late endosomes have functional plasticity, consistent with the presence of the Rab5 GTPase in discrete domains on these compartments.
溶酶体在蛋白质和其他大分子的降解中发挥着核心作用。受体被转运到溶酶体进行组成性降解的机制还不太清楚。我们分析了导致 Fc 受体 FcRn 溶酶体递呈的过程。这些研究为受体递呈提供了一条新途径的支持。具体来说，与其他进入晚期内体腔内小泡的受体不同，FcRn 是从晚期内体的限制膜转移到溶酶体的，并迅速被内化到溶酶体腔中。相比之下，LAMP-1 则保留在限制膜上。受体的转移是通过晚期内体到溶酶体的管状延伸介导的，或者是通过两个参与细胞器在 kiss-and-linger 样过程中的相互作用介导的，而完全融合很少观察到。FcRn 保留在晚期内体的限制膜上，并选择性地转运到溶酶体，使得这种受体能够进行循环或降解。因此，晚期内体具有功能可塑性，这与 Rab5 GTPase 在这些隔室的离散区域存在一致。
