21.3
Sinalização à Superfície da Célula
Hormonas—ou qualquer molécula que se ligue a um receptor, conhecido como ligante—que não são lipossolúveis (são solúveis em água) não são capazes de d…
Alguns hormônios, como aqueles que são insolúveis em lipídios, como a oxitocina, não podem se difundir através da membrana celular. Em vez disso, eles devem se ligar a recetores na superfície da célula. Após a ligação, o hormônio, considerado o primeiro mensageiro, ativa uma cascata de sinalização.
Por exemplo, quando um recetor acoplado a proteína G, ou GPCR, é ativado por um primeiro mensageiro do lado de fora da membrana da célula, por dentro, uma enzima como a fosfolipase C hidrolisa a membrana fosfolipídica PIP2 em IP3 e DAG, dois segundos mensageiros diferentes. Uma vez formado, o IP3 se move da membrana celular para a membrana endoplasmática, onde se liga a um canal de cálcio controlado por IP3, liberando iões de cálcio, um terceiro segundo mensageiro, no citoplasma e induzindo mudanças, como a contração muscular. Desta forma, um hormônio pode afetar uma célula com a qual nem entra, ativando uma série de processos celulares, dependendo dos ligantes e recetores que estão presentes.
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Q1: Why can't lipid-insoluble hormones cross the cell membrane directly?
Lipid-insoluble hormones are water-soluble molecules that cannot diffuse through the hydrophobic lipid bilayer of the cell membrane. Instead, these hormones bind to receptors on the cell surface, triggering a signaling cascade that produces cellular responses without the hormone entering the cell itself.
Q2: What happens when a first messenger binds to a G protein-coupled receptor?
When a hormone binds to a G protein-coupled receptor, the alpha subunit of the G protein dissociates from the receptor, activating an intracellular enzyme like phospholipase C. This enzyme hydrolyzes the membrane phospholipid PIP2 into IP3 and DAG, which are second messengers that trigger downstream cellular responses.
Q3: How do second messengers amplify hormonal signals inside the cell?
Second messengers like IP3 and calcium ions activate multiple proteins and pathways within the cell, amplifying the initial signal from a single hormone molecule. This multi-step process creates a cascade effect where each step depends on multiple reactions, verifying proper cellular activities occur and magnifying the response.
Q4: What are the three structural domains found in cell membrane receptors?
Cell membrane receptors contain an external ligand-binding domain that recognizes hormones, a transmembrane domain that spans the cell membrane, and an internal domain that initiates cellular responses. These three portions work together to translate extracellular signals into intracellular effects without requiring hormone entry.
Q5: How do ligand-gated ion channels differ from enzyme-linked receptors?
Ligand-gated ion channels undergo conformational changes when bound to a ligand, allowing ions to pass through a channel in the transmembrane region. Enzyme-linked receptors have an intracellular domain that is either associated with an enzyme or is an enzyme itself, directly activating other proteins when ligands bind.
Q6: What is signal transduction and why is it a multi-step process?
Signal transduction is the conversion of an extracellular stimulus into an intracellular response through multiple molecular interactions. Each step depends on other reactions, providing verification that proper cellular activities occur and allowing the response to be amplified before reaching the target outcome.
Q7: How can a hormone affect a cell without entering it?
Water-soluble hormones bind to cell surface receptors, triggering intracellular signaling cascades through second messengers like calcium ions. These messengers activate cellular processes such as muscle contraction depending on the ligands and receptors present, allowing hormones to produce effects without crossing the cell membrane. Understanding these mechanisms is central to the stress response and hypothalamic pituitary axis.