Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Biozentrum, University of Basel, 4001 Basel, Switzerland.
Genetics. 2021 Nov 5;219(3). doi: 10.1093/genetics/iyab132.
The Patched-related superfamily of transmembrane proteins can transport lipids or other hydrophobic molecules across cell membranes. While the Hedgehog receptor Patched has been intensively studied, much less is known about the biological roles of other Patched-related family members. Caenorhabditis elegans has a large number of Patched-related proteins, despite lacking a canonical Hedgehog pathway. Here, we show that PTR-4 promotes the assembly of the precuticle apical extracellular matrix, a transient and molecularly distinct matrix that precedes and patterns the later collagenous cuticle or exoskeleton. ptr-4 mutants share many phenotypes with precuticle mutants, including defects in eggshell dissolution, tube shaping, alae (cuticle ridge) structure, molting, and cuticle barrier function. PTR-4 localizes to the apical side of a subset of outward-facing epithelia, in a cyclical manner that peaks when precuticle matrix is present. Finally, PTR-4 is required to limit the accumulation of the lipocalin LPR-3 and to properly localize the Zona Pellucida domain protein LET-653 within the precuticle. We propose that PTR-4 transports lipids or other hydrophobic components that help to organize the precuticle and that the cuticle and molting defects seen in ptr-4 mutants result at least in part from earlier disorganization of the precuticle.
Patched 相关跨膜蛋白超家族可将脂质或其他疏水分子转运穿过细胞膜。尽管 Hedgehog 受体 Patched 已得到深入研究，但对其他 Patched 相关家族成员的生物学功能知之甚少。秀丽隐杆线虫拥有大量的 Patched 相关蛋白，尽管缺乏典型的 Hedgehog 途径。在这里，我们表明 PTR-4 促进了前角质层顶外细胞外基质的组装，该基质是一种短暂且分子上不同的基质，先于并塑造后来的胶原质角质层或外骨骼。ptr-4 突变体与前角质层突变体具有许多表型，包括卵壳溶解、管形成、翅（角质层脊）结构、蜕皮和角质层屏障功能缺陷。PTR-4 以上皮细胞向外一侧的子集的顶侧周期性定位，在存在前角质层基质时达到峰值。最后，PTR-4 被要求限制脂联素 LPR-3 的积累，并在正确的位置定位 Zona Pellucida 结构域蛋白 LET-653 在前角质层内。我们提出 PTR-4 运输脂质或其他疏水性成分，有助于组织前角质层，并且 ptr-4 突变体中观察到的角质层和蜕皮缺陷至少部分是由于前角质层更早的紊乱造成的。
