Rab11-FIP1A regulates early trafficking into the recycling endosomes

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• 作者：Jenny C. Schafer^a ; ^c ; Rebecca E. McRae^a ; ^b ; ^c ; Elizabeth H. Manning^a ; ^c ; Lynne A. Lapierre^a ; ^c ; James R. Goldenring^a ; ^b ; ^c ; ^d ; ^{jim.goldenring@vanderbilt.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Rab11-FIP1 ; Rab11-FIP2 ; Rab11-FIP5 ; Rab11 ; Rab11a ; Rab8a ; Rab14 ; Rab4 ; Rab5 ; EEA1 ; Membrane recycling ; Endocytosis
• 刊名：Experimental Cell Research
• 出版年：2016
• 出版时间：15 January 2016
• 年：2016
• 卷：340
• 期：2
• 页码：259-273
• 全文大小：9885 K

文摘

The Rab11 family of small GTPases, along with the Rab11-family interacting proteins (Rab11-FIPs), are critical regulators of intracellular vesicle trafficking and recycling. We have identified a point mutation of Threonine-197 site to an Alanine in Rab11-FIP1A, which causes a dramatic dominant negative phenotype when expressed in HeLa cells. The normally perinuclear distribution of GFP-Rab11-FIP1A was condensed into a membranous cisternum with almost no GFP-Rab11-FIP1A(T197A) remaining outside of this central locus. Also, this condensed GFP-FIP1A(T197A) altered the distribution of proteins in the Rab11a recycling pathway including endogenous Rab11a, Rab11-FIP1C, and transferrin receptor (CD71). Furthermore, this condensed GFP-FIP1A(T197A)-containing structure exhibited little movement in live HeLa cells. Expression of GFP-FIP1A(T197A) caused a strong blockade of transferrin recycling. Treatment of cells expressing GFP-FIP1A(T197A) with nocodazole did not disperse the Rab11a-containing recycling system. We also found that Rab5 and EEA1 were accumulated in membranes by GFP-Rab11-FIP1A but Rab4 was unaffected, suggesting that a direct pathway may exist from early endosomes into the Rab11a-containing recycling system. Our study of a potent inhibitory trafficking mutation in Rab11-FIP1A shows that Rab11-FIP1A associates with and regulates trafficking at an early step in the process of membrane recycling.