细胞生物.12 | Cell Communication

1. Origin of Eukaryotic Organelles 真核细胞细胞器起源

Endosymbiotic theory 内共生学说 (Lynn Margulis, 1970):
Mitochondria and chloroplasts originated from ancestral prokaryotes engulfed by early eukaryotes.
线粒体和叶绿体起源于被早期真核细胞吞入的原核生物。
Evidence 证据: They contain their own DNA but depend on nuclear-encoded proteins.
证据：它们含有自身DNA，但高度依赖核基因编码的蛋白质。

Cells communicate by: 细胞通过以下方式通讯：

Secreted molecules 分泌信号分子
- Autocrine 自分泌
- Paracrine 旁分泌
- Endocrine 内分泌（激素）
- Synaptic 突触信号传递
- Neuroendocrine 神经-内分泌
Direct contact 直接接触
- Cell–cell adhesion 细胞-细胞粘附
- Cell–ECM adhesion 细胞-基质粘附
Gap junctions 缝隙连接 – Direct exchange of ions/small molecules. 离子/小分子直接交换。
Extracellular vesicles 细胞外囊泡 – Carry proteins, RNAs, lipids. 携带蛋白质、RNA、脂类。
Mechanotransduction 力传导 – Mechanosensitive ion channels convert mechanical forces into biochemical signals.
机械敏感性离子通道将机械力转化为生化信号。
- Example: Hair cells in cochlea detect sound waves. 例：耳蜗毛细胞感受声波。

Signal amplification 信号放大 – One ligand → multiple downstream signals. 一个配体 → 多级放大。
Integration of signals 信号整合 – Cells combine multiple inputs. 细胞整合多种信号。
Adaptation/desensitization 适应/脱敏 – Receptors can be internalized, inactivated, or degraded. 受体可内吞、失活或降解。

Largest family (~1000 members). 最大受体家族。
7 transmembrane α-helices. 七次跨膜结构。
Work via heterotrimeric G-proteins (α, β, γ subunits). 通过异三聚体G蛋白发挥作用。
Pathways 信号通路:
- Gαs → activates adenylyl cyclase → cAMP → PKA → CREB transcription.
- Gαi → inhibits adenylyl cyclase.
- Gαq → activates PLC-β → IP3 + DAG → Ca²⁺ release + PKC.
- Gα12/13 → regulates Rho GTPases → actin cytoskeleton.

Mainly receptor tyrosine kinases (RTKs). 主要是受体酪氨酸激酶。
Mechanism: Ligand binding → dimerization → autophosphorylation. 配体结合 → 二聚化 → 自磷酸化。
Example pathway: Ras–MAP kinase cascade
- Ras → Raf (MAPKKK) → MEK (MAPKK) → ERK (MAPK) → Cell proliferation.
- Ras–MAP 激酶级联反应促进细胞增殖。

Activated by hydrophobic ligands (steroids, thyroid hormones, vitamin D, retinoids). 由疏水性配体激活。
Types:
1. Cytosolic receptors – move to nucleus after ligand binding. 胞质型，结合配体后进入细胞核。
2. Nuclear receptors – bound to DNA, activated upon ligand binding. 核内型，结合配体后激活。
Mechanism: Act as transcriptional repressors or activators. 作为转录抑制或激活因子。

Overactivation → cancer (e.g. Ras mutation). 过度激活 → 癌症（如Ras突变）。
Inflammatory molecules (prostaglandins) – inhibited by aspirin/ibuprofen. 炎症分子被阿司匹林/布洛芬抑制。
Corticosteroids inhibit PLA2, blocking prostaglandin production. 糖皮质激素抑制PLA2，阻断炎症反应。