Arginine topology controls escape of minimally cationic proteins from early endosomes to the cytoplasm.
Arginine topology controls escape of minimally cationic proteins from early endosomes to the cytoplasm.
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DOI：
10.1016/j.chembiol.2012.05.022
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发表时间：
2012-07-27
影响因子：
--
通讯作者：
Schepartz A
中科院分区：
文献类型：
--
作者：
Appelbaum JS;LaRochelle JR;Smith BA;Balkin DM;Holub JM;Schepartz A
蛋白质代表了一个不断扩大的治疗类别，但它们的作用主要限于细胞外靶点，因为大多数肽分子不能进入细胞。在这里，我们确定了两个小蛋白，微型蛋白5.3和锌指模块ZF 5.3，进入细胞，通过快速内化和从Rab5+内体逃逸到达胞质溶胶。为这些分子绘制的运输途径不同于达特和Arg8的运输途径，其需要运输超出Rab5+内体以获得胞质进入。我们的研究结果表明，5.3和ZF5.3从早期内体逃逸的能力是一个独特的特征，并意味着存在不同的信号，在短序列内编码，有利于早期与晚期内体释放。识别这些信号并理解其机制基础将说明细胞如何控制内吞货物的运动，并可能使研究人员能够设计分子以遵循快速胞质访问的所需传递途径。
Proteins represent an expanding class of therapeutics, but their actions are limited primarily to extracellular targets because most peptidic molecules fail to enter cells. Here we identified two small proteins, miniature protein 5.3 and zinc finger module ZF5.3, that enter cells to reach the cytosol through rapid internalization and escape from Rab5+ endosomes. The trafficking pathway mapped for these molecules differs from that of Tat and Arg8, which require transport beyond Rab5+ endosomes to gain cytosolic access. Our results suggest that the ability of 5.3 and ZF5.3 to escape from early endosomes is a unique feature and imply the existence of distinct signals, encodable within short sequences, that favor early versus late endosomal release. Identifying these signals and understanding their mechanistic basis will illustrate how cells control the movement of endocytic cargo and may allow researchers to engineer molecules to follow a desired delivery pathway for rapid cytosolic access.
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影响因子：
56.9
作者：
Cole, NB;Smith, CL;LippincottSchwartz, J
通讯作者：
LippincottSchwartz, J
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
15
作者：
Gemperli, AC;Rutledge, SE;Schepartz, A
通讯作者：
Schepartz, A
DOI：
10.1007/978-1-60761-919-2_38
发表时间：
2011-01-01
期刊：
CELL-PENETRATING PEPTIDES: METHODS AND PROTOCOLS
影响因子：
--
作者：
Johnson, Randolph M.;Harrison, Stephen D.;Maclean, Derek
通讯作者：
Maclean, Derek
DOI：
10.1073/pnas.78.7.4175
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BLUNDELL, TL;PITTS, JE;WU, CW
通讯作者：
WU, CW