Cells remodel their cytoskeletal networks to adapt to their environment. Here, we analyze the mechanisms utilized by the cell to tailor its microtubule landscape in response to changes in osmolarity that alter macromolecular crowding. By integrating live-cell imaging, ex vivo enzymatic assays, and in vitro reconstitution, we probe the impact of cytoplasmic density on microtubule-associated proteins (MAPs) and tubulin posttranslational modifications (PTMs). We find that human epithelial cells respond to fluctuations in cytoplasmic density by modulating microtubule acetylation, detyrosination, or MAP7 association without differentially affecting polyglutamylation, tyrosination, or MAP4 association. These MAP-PTM combinations alter intracellular cargo transport, enabling the cell to respond to osmotic challenges. We further dissect the molecular mechanisms governing tubulin PTM specification and find that MAP7 promotes acetylation and inhibits detyrosination. Our data identify MAP7 in modulating the tubulin code, resulting in microtubule cytoskeleton remodeling and alteration of intracellular transport as an integrated mechanism of cellular adaptation.

细胞重塑其细胞骨架网络以适应环境。在这里，我们分析了细胞利用的机制来调整其微管景观，以响应改变大分子拥挤的渗透压变化。通过整合活细胞成像、离体酶测定和体外重建，我们探讨了细胞质密度对微管相关蛋白（MAP）和微管蛋白翻译后修饰（PTM）的影响。我们发现人类上皮细胞通过调节微管乙酰化、脱酪氨酸或 MAP7 关联来响应细胞质密度的波动，而不会差异影响多谷氨酰化、酪氨酸化或 MAP4 关联。这些 MAP-PTM 组合改变细胞内货物运输，使细胞能够应对渗透挑战。我们进一步剖析了控制微管蛋白 PTM 规范的分子机制，发现 MAP7 促进乙酰化并抑制去酪氨酸化。我们的数据确定 MAP7 可以调节微管蛋白代码，从而导致微管细胞骨架重塑和细胞内运输的改变，作为细胞适应的综合机制。