Cell Junctions & Apoptosis 细胞连接与凋亡

1. Cell Junctions 细胞连接

Morpho-functional polarity（形态功能极性）

细胞极性保证了不同方向的功能分化。

Found only in vertebrates. 只存在于脊椎动物。
Membrane fusion-like, impermeable. 类似膜融合，不可渗透，阻止液体通过。
Located at apical region of epithelial cells. 位于上皮细胞顶端区域。
Maintain polarity by separating apical and basal domains. 通过区分顶端和基底维持极性。
Composed of claudins, occludins, tricellulin, JAM; linked to actin cytoskeleton via ZO proteins. 由封闭蛋白家族组成并与肌动蛋白骨架相连。
Function: Barrier & selective permeability. 功能：屏障 & 选择性通透性。
Can be found mainly at the apical region of epithelial cells, e.g. in the GI tracts(small intestine epithelium) and blood-brain barrier

Belt-like junction (20–25 nm). 带状结构。
Two complexes:
1. Cadherin–Catenin complex (Ca²⁺-dependent). 钙依赖性。
2. Nectin–Afadin complex (Ca²⁺-independent). 钙非依赖性。
Connected to actin cytoskeleton. 与肌动蛋白骨架相连。
Function: Resist pulling forces, provide tissue integrity. 功能：抵抗拉力，维持组织完整性。
Important in Epithelial–Mesenchymal Transition (EMT). 在上皮-间质转化中很重要。
Can be found in pithelial tissues (e.g. skin epithelium) and cardiac muscle (intercalated discs)

Spot-like junctions. 斑点状连接。
Composed of desmogleins, desmocollins (cadherin family), connected to intermediate filaments via desmoplakin.
Present in tissues under mechanical stress (epidermis, cardiac muscle, bladder). 出现在高机械应力的组织。
Function: Very resistant to pulling. 功能：高度抗拉。
Can be found in tissues under mechanical stress, such as epidermis, cardiac muscle, and bladder epithelium.

Allow passive diffusion of ions and small molecules. 允许离子和小分子扩散。
Made of connexins, forming connexons (channels). 由连接蛋白形成通道。
Function: Metabolic & electrical coupling between cells. 功能：细胞间代谢 & 电性耦合。
Can be found in in cardiac muscle and smooth muscle for electrical coupling, and also in many epithelia for metabolic cooperation.

Hemidesmosomes: Anchor epithelial cells to basal lamina via integrins + laminin + intermediate filaments.
Focal adhesions: Dynamic, link integrins to actin cytoskeleton; mediate migration, proliferation, signaling via FAK (Focal Adhesion Kinase).
Function: Anchorage dependence (cells need adhesion to survive & proliferate). 功能：依附依赖。
Anchor epithelial cells to the basement membrane, e.g. epidermal basal cells

Definition: Programmed cell death, crucial for development, tissue homeostasis, stress response. 定义：程序性细胞死亡。

Examples 实例

Cysteine–aspartic proteases. 高度特异性。
Exist as inactive procaspases, activated by proteolysis. 以无活性的前体形式存在。
Cascade activation → amplification of apoptosis signal. 级联激活 → 信号放大。
Executioner caspases (Casp-3, -6, -7) target structural proteins & DNA repair enzymes. 执行者酶切割结构蛋白和DNA修复蛋白。

Intrinsic (mitochondrial 内源性):
- Trigger: DNA damage (via p53), stress, high Ca²⁺.
- Key: Cytochrome c release → Apaf1 → Caspase-9 → Caspase-3.
Extrinsic (death receptor 外源性):
- Trigger: Fas ligand (FasL) or TNF binding receptors.
- Caspase-8 activation → BID cleavage → mitochondrial amplification.

Bcl-2 family proteins:
- Anti-apoptotic: Bcl-2, Bcl-XL. 阻止细胞色素c释放。
- Pro-apoptotic: Bax, Bak, Bad, Bid. 促进细胞色素c释放。
p53: Tumor suppressor; induces apoptosis when DNA is damaged. 抑癌基因p53在DNA损伤时触发凋亡。
Defects in apoptosis → cancer (too little apoptosis) or neurodegeneration (too much apoptosis). 凋亡缺陷 → 癌症或神经退行性疾病。