Localizations of endogenous APP/APP-proteolytic products are consistent with microtubular transport.
Localizations of endogenous APP/APP-proteolytic products are consistent with microtubular transport.
复制标题
内源性 APP/APP 蛋白水解产物的定位与微管运输一致。
DOI：
10.1007/bf02686118
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Hu,Qubai
中科院分区：
文献类型：
--
作者：
Zitnik,Galynn;Wang,Lin;Martin,GeorgeM;Hu,Qubai
Dementia of the Alzheimer type (DAT) is associated with the accumulation of β-amyloid (Aβ) peptides derived from β-amyloid precursor protein (APP). Goldstein and coworkers have suggested that APP acts as a cargo receptor connecting post-Golgi vesicles and motor proteins. Sisodia and colleagues have suggested that APP is a passive passenger within the vesicles. Both views predict that one should be able to visualize colocalizations of APP with microtubules, the object of the present investigation. To avoid possible artifacts created by APP overexpression, we studied endogenous expression in a human neuroblas toma cell line (SK-N-SH). Using high-resolution fluorescence microscopy and antibodies specific for the amino termini of APP and Aβ sequences, we found that endogenous APP and Aβ peptide immunoreactivities colocalized with microtubules in interphase cells. Disruption of microtubules, followed by fixation at various time points during repolymerization, allowed us to observe the sequence and timing of these colocalizations in interphase cells. In addition, to our surprise, we found that Aβ immunoreactivities colocalize with the mitotic spindle, a bundle of specialized microtubules. Because of the condensed cytoplasm found in neurons, we suggest that SK-N-SH cells might be a more convenient experimental system for exploring the mechanisms that underlie these protein localizations and the pathology that might result from altered APP protein structure and function.
