The Mary Babb Randolph Cancer Center and the Department of Cancer Cell Biology, West Virginia University, Morgantown, WV 26505, USA.
Eur J Cell Biol. 2011 May;90(5):376-89. doi: 10.1016/j.ejcb.2010.11.016. Epub 2011 Feb 18.
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.
肌动蛋白丝相关蛋白（AFAP）家族的衔接蛋白由三个成员组成：AFAP1、AFAP1L1 和 AFAP1L2/XB130，其中 AFAP1 被描述为 cSrc 结合伴侣和肌动蛋白交联蛋白。对 AFAP1 的同源性搜索最近发现了 AFAP1L1，它具有相似的序列、结构域结构和细胞定位；然而，基于序列变异，AFAP1L1 被假设具有独特的功能，与 AFAP1 不同。虽然 AFAP1 能够通过其 N 端 SH3 结合基序与非受体酪氨酸激酶 cSrc 的 SH3 结构域结合，但它无法与 cortactin 结合。然而，AFAP1L1 的 SH3 结合基序更有效地与 cortactin 的 SH3 结构域相互作用，而不是 cSrc。荧光显微镜显示 AFAP1L1 装饰肌动蛋白丝，并移动到点状肌动蛋白结构，与 cortactin 共定位，与侵入小体的定位一致。在 A7r5 细胞中过表达时，AFAP1L1 能够在没有刺激的情况下诱导足突形成并移动到足突。AFAP1L1 在人组织中的免疫组织化学分析显示，与 AFAP1 相比具有不同的表达，AFAP1L1 定位于肌肉和大脑齿状核的独特部位，而在这些部位无法检测到 AFAP1。我们假设 AFAP1L1 可能在影响肌动蛋白丝的变化和与结合伴侣的桥接相互作用方面发挥与 AFAP1 相似的作用，但我们假设 AFAP1L1 可能形成独特的蛋白质相互作用，在这些相互作用中，AFAP1 的效率较低，这些相互作用可能允许 AFAP1L1 影响侵入小体的形成。
