Kutzleb C, Sanders G, Yamamoto R, Wang X, Lichte B, Petrasch-Parwez E, Kilimann M W
Institut für Physiologische Chemie, Ruhr-Universität Bochum, D-44780 Bochum, Germany.
J Cell Biol. 1998 Nov 2;143(3):795-813. doi: 10.1083/jcb.143.3.795.
We report the identification and initial characterization of paralemmin, a putative new morphoregulatory protein associated with the plasma membrane. Paralemmin is highly expressed in the brain but also less abundantly in many other tissues and cell types. cDNAs from chicken, human, and mouse predict acidic proteins of 42 kD that display a pattern of sequence cassettes with high inter-species conservation separated by poorly conserved linker sequences. Prenylation and palmitoylation of a COOH-terminal cluster of three cysteine residues confers hydrophobicity and membrane association to paralemmin. Paralemmin is also phosphorylated, and its mRNA is differentially spliced in a tissue-specific and developmentally regulated manner. Differential splicing, lipidation, and phosphorylation contribute to electrophoretic heterogeneity that results in an array of multiple bands on Western blots, most notably in brain. Paralemmin is associated with the cytoplasmic face of the plasma membranes of postsynaptic specializations, axonal and dendritic processes and perikarya, and also appears to be associated with an intracellular vesicle pool. It does not line the neuronal plasmalemma continuously but in clusters and patches. Its molecular and morphological properties are reminiscent of GAP-43, CAP-23, and MARCKS, proteins implicated in plasma membrane dynamics. Overexpression in several cell lines shows that paralemmin concentrates at sites of plasma membrane activity such as filopodia and microspikes, and induces cell expansion and process formation. The lipidation motif is essential for this morphogenic activity. We propose a function for paralemmin in the control of cell shape, e.g., through an involvement in membrane flow or in membrane-cytoskeleton interaction.
我们报道了一种假定的与质膜相关的新型形态调节蛋白——副勒明蛋白（paralemmin）的鉴定及初步特性研究。副勒明蛋白在脑中高表达，但在许多其他组织和细胞类型中表达量较低。鸡、人和小鼠的cDNA预测其为42kD的酸性蛋白，该蛋白呈现出序列盒模式，种间保守性高，由保守性差的连接序列分隔。COOH末端三个半胱氨酸残基簇的异戊二烯化和棕榈酰化赋予副勒明蛋白疏水性并使其与膜结合。副勒明蛋白也被磷酸化，其mRNA以组织特异性和发育调控的方式进行差异剪接。差异剪接、脂化和磷酸化导致电泳异质性，从而在蛋白质免疫印迹上产生一系列多条带，在脑中尤为明显。副勒明蛋白与突触后特化、轴突和树突突起以及核周体的质膜胞质面相关，并且似乎也与细胞内囊泡池相关。它不是连续地排列在神经元质膜上，而是呈簇状和斑块状。其分子和形态学特性让人联想到与质膜动力学相关的GAP - 43、CAP - 23和MARCKS蛋白。在几种细胞系中的过表达表明，副勒明蛋白集中在质膜活性部位，如丝状伪足和微棘，并诱导细胞扩张和突起形成。脂化基序对于这种形态发生活性至关重要。我们提出副勒明蛋白在控制细胞形状方面具有功能，例如通过参与膜流动或膜 - 细胞骨架相互作用。
