Figure 19-27 Plasmodesmata. (A) The cytoplasmic channels of plasmodesmata pierce the plant cell wall and connect cells in a plant together. (B) Each plasmodesma is lined with plasma membrane that is common to the two connected cells. It usually also contains a fine tubular structure, the desmotubule, derived from smooth endoplasmic reticulum. (C) Electron micrograph of a longitudinal section of a plasmodesma from a water fern. The plasma membrane lines the pore and is continuous from one cell to the next. Endoplasmic reticulum and its association with the central desmotubule can also be seen. (D) A similar plasmodesma seen in cross section. (C and D, from R. Overall, J. Wolfe and B.E.S. Gunning, in Protoplasma 111, pp. 134-150. Heidelberg: Springer-Verlag, 1982.)
图 19-27 Plasmodesmata。（A）胞间层的细胞质通道刺穿植物细胞壁并将植物中的细胞连接在一起。（B）每个胞间膜都衬有两个连接细胞共有的质膜。它通常还包含一个细小的管状结构，即桥部，来源于光滑的内质网。（C）水蕨等胞胎纵向切片的电子显微照片。质膜排列在孔中，从一个细胞到另一个细胞是连续的。还可见内质网及其与中央桥节的关联。（D） 在横截面上观察到类似的等离子体。（C 和 D，摘自 R. Overall、J. Wolfe 和 B.E.S. Gunning，原生原体 111，第 134-150 页。海德堡：Springer-Verlag，1982 年。

is similar to the molecular-weight cutoff for gap junctions. As with gap junctions, transport through plasmodesmata is regulated. Dye-injection experiments, for example, show that there can be barriers to the movement of even low-molecularweight molecules between certain cells, or groups of cells, that are connected by apparently normal plasmodesmata; the mechanisms that restrict communication in these cases are not understood.
类似于间隙连接的分子量临界值。与间隙连接一样，通过胞间膜的转运受到调节。例如，染料注射实验表明，即使是低分子量分子在某些细胞或细胞群之间的运动也可能存在障碍，这些细胞或细胞群由明显正常的胞间洲连接;在这些情况下限制通信的机制尚不清楚。

We now complete our overview of cell-cell junctions and adhesion by briefly describing some of the more specialized adhesion mechanisms used in some tissues. In addition to those we have already discussed, at least three other superfamilies of cell-cell adhesion proteins are important: the integrins, the selectins, and the adhesive immunoglobulin (Ig) superfamily members. We shall discuss integrins in more detail later: their main function is in cell-matrix adhesion, but a few of them mediate cell-cell adhesion in specialized circumstances. dependence provides one simple way to distinguish among these classes of adhesion proteins experimentally. Selectins, like cadherins and integrins, require for their adhesive function; Ig superfamily members do not.
现在，我们通过简要描述某些组织中使用的一些更专业的粘附机制来完成对细胞间连接和粘附的概述。除了我们已经讨论过的那些之外，至少还有三个细胞间粘附蛋白的超家族很重要：整合素、选择素和粘附性免疫球蛋白 （Ig） 超家族成员。我们稍后将更详细地讨论整合素：它们的主要功能是细胞-基质粘附，但其中一些在特殊情况下介导细胞-细胞粘附。 依赖性提供了一种简单的方法，可以在实验上区分这些类别的粘附蛋白。选择素，如钙粘蛋白和整合素， 需要其粘附功能;Ig 超家族成员则不然。

Selectins are cell-surface carbohydrate-binding proteins (lectins) that mediate a variety of transient cell-cell adhesion interactions in the bloodstream. Their main role, in vertebrates at least, is in governing the traffic of white blood cells into normal lymphoid organs and any inflamed tissues. White blood cells lead a nomadic life, roving between the bloodstream and the tissues, and this necessitates special adhesive behavior. The selectins control the binding of white blood cells to the endothelial cells lining blood vessels, thereby enabling the blood cells to migrate out of the bloodstream into a tissue.
选择素是细胞表面碳水化合物结合蛋白（凝集素），介导血液中各种瞬时细胞间粘附相互作用。至少在脊椎动物中，它们的主要作用是控制白细胞进入正常淋巴器官和任何发炎组织。白细胞过着游牧生活，在血液和组织之间游荡，这需要特殊的粘附行为。选择素控制白细胞与血管内皮细胞的结合，从而使血细胞能够从血流中迁移到组织中。

Each selectin is a transmembrane protein with a conserved lectin domain that binds to a specific oligosaccharide on another cell (Figure 19-28A). There are at least three types: -selectin on white blood cells, -selectin on blood platelets and on endothelial cells that have been locally activated by an inflammatory response, and E-selectin on activated endothelial cells. In a lymphoid organ, such as a lymph
每种选择素都是一种跨膜蛋白，具有保守的凝集素结构域，可与另一个细胞上的特定寡糖结合（图 19-28A）。至少有三种类型： 白细胞上的选择素， 血小板和内皮细胞上的选择素，以及活化的内皮细胞上的E-选择素。在淋巴器官中，例如淋巴

plasma membrane 质膜

(A)

node or the spleen, the endothelial cells express oligosaccharides that are recognized by L-selectin on lymphocytes, causing the lymphocytes to loiter and become trapped. At sites of inflammation, the roles are reversed: the endothelial cells switch on expression of selectins that recognize the oligosaccharides on white blood cells and platelets, flagging the cells down to help deal with the local emergency. Selectins do not act alone, however; they collaborate with integrins, which strengthen the binding of the blood cells to the endothelium. The cell-cell adhesions mediated by both selectins and integrins are heterophilic-that is, the binding is to a molecule of a different type: selectins bind to specific oligosaccharides on glycoproteins and glycolipids, while integrins bind to specific Ig-family proteins.
淋巴结或脾脏，内皮细胞表达寡糖，这些寡糖在淋巴细胞上被L-选择素识别，导致淋巴细胞游荡并被困住。在炎症部位，作用被颠倒了：内皮细胞开启选择素的表达，这些选择素识别白细胞和血小板上的低聚糖，标记细胞以帮助处理局部紧急情况。然而，选择素并不单独起作用;它们与整合素合作，加强血细胞与内皮细胞的结合。由选择素和整合素介导的细胞间粘附是异嗜性的，也就是说，结合是与不同类型的分子结合：选择素与糖蛋白和糖脂上的特定寡糖结合，而整合素与特定的 Ig 家族蛋白结合。

Selectins and integrins act in sequence to let white blood cells leave the bloodstream and enter tissues (Figure 19-28B). The selectins mediate a weak adhesion because the binding of the lectin domain of the selectin to its carbohydrate ligand is of low affinity. This allows the white blood cell to adhere weakly and reversibly to the endothelium, rolling along the surface of the blood vessel, propelled by the flow of blood. The rolling continues until the blood cell activates its integrins. As we discuss later, these transmembrane molecules can be switched into an adhesive conformation that enables them to latch onto specific macromolecules external to the cell-in the present case, proteins on the surfaces of the endothelial cells. Once it has attached in this way, the white blood cell escapes from the bloodstream into the tissue by crawling out of the blood vessel between adjacent endothelial cells.
选择素和整合素依次起作用，让白细胞离开血流进入组织（图19-28B）。选择素介导弱粘附，因为选择素的凝集素结构域与其碳水化合物配体的结合亲和力低。这使得白细胞在血液流动的推动下，弱而可逆地粘附在内皮上，沿着血管表面滚动。滚动一直持续到血细胞激活其整合素。正如我们稍后讨论的那样，这些跨膜分子可以转换为粘附构象，使它们能够锁定在细胞外部的特定大分子上 - 在本例中，内皮细胞表面的蛋白质。一旦它以这种方式附着，白细胞就会从血流中逃逸到组织中，从相邻内皮细胞之间的血管中爬出。

The chief endothelial cell proteins that are recognized by the white blood cell integrins are called ICAMs (intercellular cell adhesion molecules) or VCAMs (vascular cell adhesion molecules). They are members of another large and ancient family of cell-surface molecules-the immunoglobulin (Ig) superfamily. These contain one or more extracellular Ig-like domains that are characteristic of antibody molecules. They have many functions outside the immune system that are unrelated to immune defenses.
白细胞整合素识别的主要内皮细胞蛋白称为ICAM（细胞间细胞粘附分子）或VCAM（血管细胞粘附分子）。它们是另一个庞大而古老的细胞表面分子家族——免疫球蛋白（Ig）超家族的成员。它们包含一个或多个细胞外 Ig 样结构域，这些结构域是抗体分子的特征。它们在免疫系统之外具有许多与免疫防御无关的功能。

While ICAMs and VCAMs on endothelial cells both mediate heterophilic binding to integrins, many other Ig superfamily members appear to mediate homophilic binding. An example is the neural cell adhesion molecule (NCAM), which is expressed by various cell types, including most nerve cells, and can take different forms, generated by alternative splicing of an RNA transcript produced from a single gene (Figure 19-29). Some forms of NCAM carry an unusually large
虽然内皮细胞上的 ICAM 和 VCAM 都介导与整合素的异嗜性结合，但许多其他 Ig 超家族成员似乎介导同亲性结合。一个例子是神经细胞粘附分子 （NCAM），它由各种细胞类型（包括大多数神经细胞）表达，并且可以采取不同的形式，通过对单个基因产生的 RNA 转录物进行选择性剪接产生（图 19-29）。某些形式的 NCAM 携带异常大的
Figure 19-28 The structure and function of selectins. (A) The structure of P-selectin. The selectin attaches to the actin cytoskeleton through adaptor proteins that are still poorly characterized. (B) How selectins and integrins mediate the cell-cell adhesions required for a white blood cell to migrate out of the bloodstream into a tissue. First, selectins on endothelial cells bind to oligosaccharides on the white blood cell, so that it becomes loosely attached and rolls along the vessel wall. Then the white blood cell activates a cellsurface integrin called LFA1, which binds to a protein called ICAM1 (belonging to the lg superfamily) on the membrane of the endothelial cell. The white blood cell adheres to the vessel wall and then crawls out of the vessel by a process that requires another immunoglobulin superfamily member called PECAM1 (or CD31), not shown (Movie 19.2). EGF, epidermal growth factor.
图19-28 选择素的结构和功能。（A）P-选择素的结构。选择素通过衔接蛋白附着在肌动蛋白细胞骨架上，而衔接蛋白的表征仍然很差。（B） 选择素和整合素如何介导白细胞从血流迁移到组织所需的细胞间粘附。首先，内皮细胞上的选择素与白细胞上的寡糖结合，使其松散地附着并沿着血管壁滚动。然后白细胞激活一种叫做LFA1的细胞表面整合素，它与内皮细胞膜上一种叫做ICAM1（属于lg超家族）的蛋白质结合。白细胞粘附在血管壁上，然后通过一个过程爬出血管，这个过程需要另一个称为PECAM1（或CD31）的免疫球蛋白超家族成员，未显示（电影19.2）。EGF，表皮生长因子。

quantity of sialic acid (with chains containing hundreds of repeating sialic acid units). By virtue of their negative charge, the long polysialic acid chains can interfere with cell adhesion (because like charges repel one another); thus, these forms of NCAM can serve to inhibit adhesion, rather than cause it.
唾液酸的数量（含有数百个重复唾液酸单元的链）。由于它们的负电荷，长多唾液酸链会干扰细胞粘附（因为类似电荷会相互排斥）;因此，这些形式的NCAM可以抑制粘连，而不是引起粘连。

A cell of a given type generally uses an assortment of different adhesion proteins to interact with other cells, just as each cell uses an assortment of different receptors to respond to the many soluble extracellular signal molecules in its environment. Although cadherins and Ig superfamily members are frequently expressed on the same cells, the adhesions mediated by cadherins are much stronger, and they are largely responsible for holding cells together, segregating cell collectives into discrete tissues, and maintaining tissue integrity. Molecules such as NCAM seem to contribute more to the fine-tuning of these adhesive interactions during development and regeneration, playing a part in various specialized adhesive phenomena, such as that discussed for blood cells and endothelial cells. Thus, while mutant mice that lack -cadherin die early in development, those that lack NCAM develop relatively normally but show some mild abnormalities in the development of certain specific tissues, including parts of the nervous system.
给定类型的细胞通常使用各种不同的粘附蛋白与其他细胞相互作用，就像每个细胞使用各种不同的受体来响应其环境中的许多可溶性细胞外信号分子一样。虽然钙粘蛋白和Ig超家族成员经常在同一细胞上表达，但钙粘蛋白介导的粘附要强得多，它们主要负责将细胞保持在一起，将细胞集合分离成离散的组织，并维持组织完整性。NCAM等分子似乎在发育和再生过程中对这些粘附相互作用的微调贡献更大，在各种特殊的粘附现象中发挥作用，例如讨论的血细胞和内皮细胞。因此，虽然缺乏 钙粘蛋白的突变小鼠在发育早期死亡，但缺乏NCAM的突变小鼠发育相对正常，但在某些特定组织（包括神经系统的一部分）的发育中表现出一些轻微的异常。

In epithelia, as well as in some other types of tissue, cells are directly attached to one another through strong cell-cell adhesions, mediated by transmembrane proteins called cadherins, which are anchored intracellularly to the cytoskeleton. Cadherins generally bind to one another homophilically: the head of one cadherin molecule binds to the head of a similar cadherin on an opposite cell. This selectivity enables mixed populations of cells of different types to sort out from one another according to the specific cadherins they express, and it helps to control cell rearrangements during development.
在上皮细胞以及一些其他类型的组织中，细胞通过强烈的细胞间粘附直接相互附着，由称为钙粘蛋白的跨膜蛋白介导，钙粘蛋白在细胞内锚定在细胞骨架上。钙粘蛋白通常以同质方式相互结合：一个钙粘蛋白分子的头部与相反细胞上类似钙粘蛋白的头部结合。这种选择性使不同类型的混合细胞群能够根据它们表达的特定钙粘蛋白相互分拣，并且有助于控制发育过程中的细胞重排。

The "classical" cadherins at adherens junctions are linked to the actin cytoskeleton by intracellular adaptor proteins called catenins. These form an anchoring complex on the intracellular tail of the cadherin molecule, and are involved not only in physical anchorage but also in the detection of and response to tension and other regulatory signals at the junction.
粘附连接处的“经典”钙粘蛋白通过称为连环蛋白的细胞内衔接蛋白与肌动蛋白细胞骨架相连。它们在钙粘蛋白分子的细胞内尾部形成锚定复合物，不仅参与物理锚定，还参与检测和响应连接处的张力和其他调节信号。

Tight junctions seal the gaps between cells in epithelia, creating a barrier to the diffusion of molecules across the cell sheet and also helping to separate the populations of proteins in the apical and basolateral plasma membrane domains of the epithelial cell. Claudins are the major transmembrane proteins forming gap junctions. Intracellular scaffold proteins organize the claudins and other junctional proteins into a complex protein network that is linked to the actin cytoskeleton.
紧密连接密封了上皮细胞之间的间隙，为分子在细胞片中的扩散创造了屏障，也有助于分离上皮细胞顶端和基底外侧质膜结构域中的蛋白质群。Claudins 是形成间隙连接的主要跨膜蛋白。细胞内支架蛋白将 claudin 和其他连接蛋白组织成与肌动蛋白细胞骨架相连的复杂蛋白质网络。
Figure 19-29 Two members of the Ig superfamily of cell-cell adhesion molecules. NCAM is expressed on neurons and many other cell types, and mediates homophilic binding. ICAM is expressed on endothelial cells and some other cell types and binds heterophilically to an integrin on white blood cells. Both NCAM and ICAM are glycoproteins, but their attached carbohydrate chains are not shown
图 19-29 细胞间粘附分子 Ig 超家族的两个成员。NCAM在神经元和许多其他细胞类型上表达，并介导同亲性结合。ICAM在内皮细胞和其他一些细胞类型上表达，并与白细胞上的整合素异嗜结合。NCAM 和 ICAM 都是糖蛋白，但它们的连接碳水化合物链未显示

The cells of many animal tissues are coupled by gap junctions, which take the form of plaques of clustered connexons, which usually allow molecules smaller than about 1000 daltons to pass directly from the inside of one cell to the inside of the next. Cells connected by gap junctions share many of their inorganic ions and other small molecules and are therefore chemically and electrically coupled.
许多动物组织的细胞通过间隙连接偶联，间隙连接以簇状连接子的斑块形式出现，通常允许小于约1000道尔顿的分子直接从一个细胞内部传递到下一个细胞内部。通过间隙连接连接的细胞共享许多无机离子和其他小分子，因此在化学和电偶联上。

Three additional classes of transmembrane adhesion proteins mediate more transient cell-cell adhesion: selectins, immunoglobulin (Ig) superfamily members, and integrins. Selectins are expressed on white blood cells, blood platelets, and endothelial cells; they bind heterophilically to carbohydrate groups on cell surfaces, helping to mediate the adhesive interactions between these cells. Ig superfamily proteins also play a part in these interactions, as well as in many other adhesive processes; some of them bind homophilically, some heterophilically. Integrins, though they mainly serve to attach cells to the extracellular matrix, can also mediate cellcell adhesion by binding to specific Ig superfamily proteins.
另外三类跨膜粘附蛋白介导更短暂的细胞间粘附：选择素、免疫球蛋白 （Ig） 超家族成员和整合素。选择素在白细胞、血小板和内皮细胞上表达;它们与细胞表面的碳水化合物基团异质结合，有助于介导这些细胞之间的粘附相互作用。Ig超家族蛋白也在这些相互作用以及许多其他粘附过程中发挥作用;它们中的一些是同亲性的，一些是异性的。整合素虽然主要用于将细胞附着在细胞外基质上，但也可以通过与特定的 Ig 超家族蛋白结合来介导细胞粘附。

Tissues are not made up solely of cells. They also contain a remarkably complex and intricate network of macromolecules constituting the extracellular matrix. This matrix is composed of many different proteins and polysaccharides that are secreted locally and assembled into an organized meshwork in close association with the surfaces of the cells that produce them.
组织不仅仅由细胞组成。它们还包含构成细胞外基质的非常复杂和错综复杂的大分子网络。该基质由许多不同的蛋白质和多糖组成，这些蛋白质和多糖在局部分泌并组装成一个有组织的网状结构，与产生它们的细胞表面紧密结合。

The classes of macromolecules constituting the extracellular matrix in different animal tissues are broadly similar, but variations in the relative amounts of these different classes of molecules and in the ways in which they are organized give rise to an amazing diversity of materials. The matrix can become calcified to form the rock-hard structures of bone or teeth, or it can form the transparent substance of the cornea, or it can adopt the ropelike organization that gives tendons their enormous tensile strength. It forms the jelly in a jellyfish. Covering the body of a beetle or a lobster, it forms a rigid carapace. Moreover, the extracellular matrix is more than a passive scaffold to provide physical support. It has an active and complex role in regulating the behavior of the cells that touch it, inhabit it, or crawl through its meshes, influencing their survival, development, migration, proliferation, shape, and function.
在不同动物组织中构成细胞外基质的大分子类别大致相似，但这些不同类别的分子的相对数量及其组织方式的变化导致了材料的惊人多样性。基质可以钙化形成骨骼或牙齿的坚硬结构，或者可以形成角膜的透明物质，或者可以采用绳状组织，使肌腱具有巨大的抗拉强度。它在水母中形成水母。它覆盖在甲虫或龙虾的身体上，形成坚硬的甲壳。此外，细胞外基质不仅仅是提供物理支持的被动支架。它在调节接触它、栖息或爬过其网格的细胞的行为方面具有积极而复杂的作用，影响它们的生存、发育、迁移、增殖、形状和功能。

In this section, we describe the major features of the extracellular matrix in animal tissues, with an emphasis on vertebrates. We begin with an overview of the major classes of macromolecules in the matrix, after which we turn to the structure and function of the basal lamina, the thin layer of specialized extracellular matrix that lies beneath all epithelial cells. In the sections that follow, we then describe the varied types of cell-matrix junctions through which cells are connected to the matrix.
在本节中，我们描述了动物组织中细胞外基质的主要特征，重点是脊椎动物。我们首先概述了基质中主要类别的大分子，然后我们转向基底层的结构和功能，基底层是位于所有上皮细胞下方的专门细胞外基质的薄层。在接下来的章节中，我们将描述各种类型的细胞-基质连接，通过这些连接，细胞连接到基质。

The macromolecules that constitute the extracellular matrix are mainly produced locally by cells in the matrix. As we discuss later, these cells also help to organize the matrix: the orientation of the cytoskeleton inside the cell can control the orientation of the matrix produced outside. In most connective tissues, the matrix macromolecules are secreted by cells called fibroblasts (Figure 19-30). In certain specialized types of connective tissues, such as cartilage and bone, however, they are secreted by cells of the fibroblast family that have more specific names: chondroblasts, for example, form cartilage, and osteoblasts form bone.
构成细胞外基质的大分子主要由基质中的细胞局部产生。正如我们稍后讨论的那样，这些细胞还有助于组织基质：细胞内细胞骨架的方向可以控制外部产生的基质的方向。在大多数结缔组织中，基质大分子由称为成纤维细胞的细胞分泌（图 19-30）。然而，在某些特殊类型的结缔组织中，例如软骨和骨骼，它们是由具有更具体名称的成纤维细胞家族的细胞分泌的：例如，软骨母细胞形成软骨，成骨细胞形成骨骼。

The extracellular matrix is constructed from three major classes of macromolecules: (1) glycosaminoglycans (GAGs), which are large and highly charged polysaccharides that are usually covalently linked to protein in the form of proteoglycans; (2) fibrous proteins, which are primarily members of the collagen family; and (3) a large class of noncollagen glycoproteins, which carry conventional asparagine-linked oligosaccharides (described in Chapter 12). All three classes of macromolecule have many members and come in a great variety of shapes and
细胞外基质由三大类大分子构成：（1）糖胺聚糖（GAG），它们是大而带高电荷的多糖，通常以蛋白聚糖的形式与蛋白质共价连接;（2）纤维蛋白，主要是胶原蛋白家族的成员;（3）一大类非胶原糖蛋白，它们携带传统的天冬酰胺连接的寡糖（见第12章）。所有三类大分子都有许多成员，并且具有多种形状和

Figure 19-30 Fibroblasts in connective tissue. This scanning electron micrograph shows tissue from the cornea of a rat. The extracellular matrix surrounding the fibroblasts is here composed largely of collagen fibrils. The glycoproteins, hyaluronan, and proteoglycans, which normally form a hydrated gel filling the interstices of the fibrous network, have been removed by enzyme and acid treatment. (Courtesy of T. Nishida.)
图19-30 结缔组织中的成纤维细胞。这张扫描电子显微照片显示了大鼠角膜的组织。成纤维细胞周围的细胞外基质主要由胶原纤维组成。糖蛋白、透明质酸和蛋白聚糖通常形成水合凝胶，填充纤维网络的间隙，已被酶和酸处理去除。（图片由 T. Nishida 提供。