Microtubule nucleation at the cis-side of the Golgi apparatus requires AKAP450 and GM130.
نویسندگان
چکیده
We report that microtubule (MT) nucleation at the Golgi apparatus requires AKAP450, a centrosomal gamma-TuRC-interacting protein that also forms a distinct network associated with the Golgi. Depletion of AKAP450 abolished MT nucleation at the Golgi, whereas depletion of the cis-Golgi protein GM130 led to the disorganisation of AKAP450 network and impairment of MT nucleation. Brefeldin-A treatment induced relocalisation of AKAP450 to ER exit sites and concomitant redistribution of MT nucleation capacity to the ER. AKAP450 specifically binds the cis-side of the Golgi in an MT-independent, GM130-dependent manner. Short AKAP450-dependent growing MTs are covered by CLASP2. Like for centrosome, dynein/dynactin complexes are necessary to anchor MTs growing from the Golgi. We further show that Golgi-associated AKAP450 has a role in cell migration rather than in cell polarisation of the centrosome-Golgi apparatus. We propose that the recruitment of AKAP450 on the Golgi membranes through GM130 allows centrosome-associated nucleating activity to extend to the Golgi, to control the assembly of subsets of MTs ensuring specific functions within the Golgi or for transporting specific cargos to the cell periphery.
منابع مشابه
A new function for an old organelle: microtubule nucleation at the Golgi apparatus
The microtubule cytoskeleton of a mammalian cell originates from the perinuclear region and controls membrane trafficking, organelle positioning, and cell polarisation. Although the centrosome is viewed as the major microtubule organising centre, there is emerging evidence that the Golgi apparatus also has a role in the nucleation of perinuclear microtubules during the interphase. In a recent p...
متن کاملDisconnecting the Golgi ribbon from the centrosome prevents directional cell migration and ciliogenesis
Mammalian cells exhibit a frequent pericentrosomal Golgi ribbon organization. In this paper, we show that two AKAP450 N-terminal fragments, both containing the Golgi-binding GM130-interacting domain of AKAP450, dissociated endogenous AKAP450 from the Golgi and inhibited microtubule (MT) nucleation at the Golgi without interfering with centrosomal activity. These two fragments had, however, stri...
متن کاملA newly identified myomegalin isoform functions in Golgi microtubule organization and ER-Golgi transport.
The Golgi of mammalian cells is known to be a major microtubule-organizing site that requires microtubules for its organization and protein trafficking. However, the mechanisms underlying the microtubule organization of the Golgi remain obscure. We used immunoprecipitation coupled with mass spectrometry to identify a widely expressed isoform of the poorly characterized muscle protein myomegalin...
متن کاملMyomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules
The generation of cellular microtubules is initiated at specific sites such as the centrosome and the Golgi apparatus that contain nucleation complexes rich in γ-tubulin. The microtubule growing plus-ends are stabilized by plus-end tracking proteins (+TIPs), mainly EB1 and associated proteins. Myomegalin was identified as a centrosome/Golgi protein associated with cyclic nucleotide phosphodiest...
متن کاملPTTG1/securin modulates microtubule nucleation and cell migration
Pituitary tumor transforming gene 1 (PTTG1), also known as securin, has been implicated in many biological functions, including inhibition of sister chromatid separation, DNA repair, organ development, and regulation of the expression and secretion of angiogenic and metastatic factors. Although most of these functions of securin seem to depend on the localization of PTTG1 in the nucleus of the ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The EMBO journal
دوره 28 8 شماره
صفحات -
تاریخ انتشار 2009