The endocytic protein EHD1 plays an important role in ciliogenesis by facilitating fusion of the ciliary vesicle and removal of CP110 (also known as CCP110) from the mother centriole, as well as removal of Cep215 (also known as CDK5RAP2) from centrioles to permit disengagement and duplication. However, the mechanism of its centrosomal recruitment remains unknown. Here, we address the role of the EHD1 interaction partner MICAL-L1 in ciliogenesis. MICAL-L1 knockdown impairs ciliogenesis in a similar manner to EHD1 knockdown, and MICAL-L1 localizes to cilia and centrosomes in both ciliated and non-ciliated cells. Consistent with EHD1 function, MICAL-L1-depletion prevents CP110 removal from the mother centriole. Moreover, upon MICAL-L1-depletion, EHD1 fails to localize to basal bodies. Since MICAL-L1 localizes to the centrosome even in non-ciliated cells, we hypothesized that it might be anchored to the centrosome via an interaction with centrosomal proteins. By performing mass spectrometry, we identified several tubulins as potential MICAL-L1 interaction partners, and found a direct interaction between MICAL-L1 and both α-tubulin-β-tubulin heterodimers and γ-tubulin. Our data support the notion that a pool of centriolar γ-tubulin and/or α-tubulin-β-tubulin heterodimers anchor MICAL-L1 to the centriole, where it might recruit EHD1 to promote ciliogenesis.

中文翻译：

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MICAL-L1通过将EHD1募集至初级纤毛来协调纤毛发生。

内吞蛋白EHD1通过促进睫状小泡的融合和从母粒中去除CP110（也称为CCP110），以及从粒中去除Cep215（也称为CDK5RAP2）以允许分离和分离，在纤毛形成中发挥重要作用。复制。然而，其中心体募集的机制仍是未知的。在这里，我们解决了EHD1相互作用伴侣MICAL-L1在纤毛发生中的作用。MICAL-L1敲低以与EHD1敲低相似的方式损害纤毛发生，而MICAL-L1在纤毛和非纤毛细胞中均定位于纤毛和中心体。与EHD1功能一致，MICAL-L1耗尽可防止CP110从母粒中移除。此外，在MICAL-L1耗尽后，EHD1无法定位到基体。由于MICAL-L1即使在非纤毛细胞中也定位于中心体，因此我们假设它可能通过与中心体蛋白的相互作用而锚定于中心体。通过质谱分析，我们确定了几种微管蛋白是潜在的MICAL-L1相互作用伙伴，并发现MICAL-L1与α-微管蛋白-β-微管蛋白异二聚体和γ-微管蛋白之间存在直接相互作用。我们的数据支持以下观点：中心粒γ-微管蛋白和/或α-微管蛋白-β-微管蛋白异二聚体可将MICAL-L1锚定于中心，在此可能募集EHD1来促进纤毛发生。并且发现MICAL-L1与α-微管蛋白-β-微管蛋白异二聚体和γ-微管蛋白之间存在直接相互作用。我们的数据支持以下观点：中心粒γ-微管蛋白和/或α-微管蛋白-β-微管蛋白异二聚体可将MICAL-L1锚定于中心，在此可能募集EHD1来促进纤毛发生。并且发现MICAL-L1与α-微管蛋白-β-微管蛋白异二聚体和γ-微管蛋白之间存在直接相互作用。我们的数据支持以下观点：中心粒γ-微管蛋白和/或α-微管蛋白-β-微管蛋白异二聚体将MICAL-L1锚定于中心，在此可能募集EHD1来促进纤毛发生。