Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies.
Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies.
复制标题
DOI：
10.1091/mbc.e13-10-0617
复制
发表时间：
2014-09-15
影响因子：
3.3
通讯作者：
Rusan NM
中科院分区：
文献类型：
--
作者：
Galletta BJ;Guillen RX;Fagerstrom CJ;Brownlee CW;Lerit DA;Megraw TL;Rogers GC;Rusan NM
Pericentrin（PLP）是一种中心体蛋白，用于组织中心粒周围物质。它需要与钙调素（CaM）的相互作用，以适当的中心体靶向在体外和体内。此外，PLP-CaM相互作用对机械感觉神经元功能至关重要，但对功能性精子则不然。Pericentrin是一种重要的中心体蛋白，在有丝分裂中组织中心粒周围物质（PCM）。在pericentrin突变导致人类遗传疾病Maurisski/小头骨发育不良原始侏儒II型，使其调控的详细了解极其重要。Germaine到pericentrin在组织PCM中的功能是其通过保守的C-末端PACT结构域定位于中心体的能力。在这里，我们使用果蝇pericentrin样蛋白（PLP），以了解如何PACT域的调节。我们发现，PLP与钙调素（CaM）在两个高度保守的钙调素结合位点的PACT域控制PLP的中心体的适当目标的相互作用。用单点突变破坏PLP-CaM相互作用使得PLP在培养的S2细胞和果蝇成神经细胞中定位于中心粒的效率低下。虽然PCM的水平不受影响，但它是高度无组织的。我们还表明，在男性睾丸的基体形成和功能精子的生产不依赖于PLP-CaM的相互作用，而功能mechanosensory神经元的生产。
Pericentrin (PLP) is a centrosomal protein required for organizing pericentriolar material. It requires interaction with calmodulin (CaM) for proper centrosome targeting both in vitro and in vivo. In addition, the PLP-CaM interaction is critical for mechanosensory neuron function but not for functional sperm. Pericentrin is a critical centrosomal protein required for organizing pericentriolar material (PCM) in mitosis. Mutations in pericentrin cause the human genetic disorder Majewski/microcephalic osteodysplastic primordial dwarfism type II, making a detailed understanding of its regulation extremely important. Germaine to pericentrin's function in organizing PCM is its ability to localize to the centrosome through the conserved C-terminal PACT domain. Here we use Drosophila pericentrin-like-protein (PLP) to understand how the PACT domain is regulated. We show that the interaction of PLP with calmodulin (CaM) at two highly conserved CaM-binding sites in the PACT domain controls the proper targeting of PLP to the centrosome. Disrupting the PLP-CaM interaction with single point mutations renders PLP inefficient in localizing to centrioles in cultured S2 cells and Drosophila neuroblasts. Although levels of PCM are unaffected, it is highly disorganized. We also demonstrate that basal body formation in the male testes and the production of functional sperm does not rely on the PLP-CaM interaction, whereas production of functional mechanosensory neurons does.