AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes.
AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes.
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DOI：
10.1016/j.ejcb.2010.11.016
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发表时间：
2011-05
影响因子：
6.6
通讯作者：
Cunnick JM
中科院分区：
文献类型：
--
作者：
Snyder BN;Cho Y;Qian Y;Coad JE;Flynn DC;Cunnick JM
肌动蛋白丝相关蛋白（AFAP）家族由三个成员组成：AFAP 1，AFAP 1 L1和AFAP 1 L2/XB 130，其中AFAP 1被最好地描述为cSrc结合伴侣和肌动蛋白交联蛋白。AFAP 1的同源性搜索最近鉴定了AFAP 1 L1，其具有相似的序列、结构域结构和细胞定位;然而，基于序列变异，假设AFAP 1 L1具有不同于AFAP 1的独特功能。虽然AFAP 1具有通过N-末端SH 3结合基序结合非受体酪氨酸激酶cSrc的SH 3结构域的能力，但它不能结合coronin。然而，AFAP 1 L1的SH 3结合基序在与coronin的SH 3结构域而不是cSrc相互作用时更有效。荧光显微镜显示AFAP 1 L1装饰肌动蛋白丝，并移动到点状肌动蛋白结构，并与corneum共定位，与侵袭体定位一致。在A7 r5细胞中过表达后，AFAP 1 L1能够诱导足体形成并在没有刺激的情况下移动到足体。AFAP 1 L1在人体组织中的免疫组织化学分析显示，与AFAP 1相比，AFAP 1 L1在肌肉和脑齿状核中的独特位点定位，其中AFAP 1检测不到。我们假设AFAP 1 L1可能在影响肌动蛋白丝的变化和桥接与结合伴侣的相互作用方面发挥与AFAP 1相似的作用，但我们假设AFAP 1 L1可能形成独特的蛋白质相互作用，其中AFAP 1效率较低，这些相互作用可能允许AFAP 1 L1影响侵袭体的形成。
The actin-filament associated protein (AFAP) family of adaptor proteins consists of three members: AFAP1, AFAP1L1, and AFAP1L2/XB130 with AFAP1 being the best described as a cSrc binding partner and actin cross-linking protein. A homology search of AFAP1 recently identified AFAP1L1 which has a similar sequence, domain structure and cellular localization; however, based upon sequence variations, AFAP1L1 is hypothesized to have unique functions that are distinct from AFAP1. While AFAP1 has the ability to bind to the SH3 domain of the nonreceptor tyrosine kinase cSrc via an N-terminal SH3 binding motif, it was unable to bind cortactin. However, the SH3 binding motif of AFAP1L1 was more efficient at interacting with the SH3 domain of cortactin and not cSrc. AFAP1L1 was shown by fluorescence microscopy to decorate actin filaments and move to punctate actin structures and colocalize with cortactin, consistent with localization to invadosomes. Upon overexpression in A7r5 cells, AFAP1L1 had the ability to induce podosome formation and move to podosomes without stimulation. Immunohistochemical analysis of AFAP1L1 in human tissues shows differential expression when contrasted with AFAP1 with localization of AFAP1L1 to unique sites in muscle and the dentate nucleus of the brain where AFAP1 was not detectable. We hypothesize AFAP1L1 may play a similar role to AFAP1 in affecting changes in actin filaments and bridging interactions with binding partners, but we hypothesize that AFAP1L1 may forge unique protein interactions in which AFAP1 is less efficient, and these interactions may allow AFAP1L1 to affect invadosome formation.
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影响因子：
3.7
作者：
Qian, Y;Baisden, JM;Flynn, DC
通讯作者：
Flynn, DC
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作者：
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通讯作者：
Flynn, DC
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作者：
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作者：
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作者：
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通讯作者：
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