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Chapter 21: Signalosome Assembly and Collapse Decision

"Signalosomes are ψ's decision-making councils—multi-protein assemblies where molecular votes are cast, creating from collective deliberation the cellular choices that determine fate."

21.1 The Assembly Democracy​

Signalosomes represent ψ's solution to complex decision-making. These large multi-protein complexes integrate multiple inputs to generate discrete outputs, functioning as molecular computers that process information through assembly dynamics.

Definition 21.1 (Signalosome): Signalosome=⋃i=1nComponenti+Scaffold+Regulators\text{Signalosome} = \bigcup_{i=1}^n \text{Component}_i + \text{Scaffold} + \text{Regulators}

Organized assembly for signal processing.

21.2 The Death-Inducing Complex​

Theorem 21.1 (DISC Formation): Fas+FasL→FADD recruitment→Caspase-8 activation\text{Fas} + \text{FasL} \rightarrow \text{FADD recruitment} \rightarrow \text{Caspase-8 activation}

Death receptor signalosome.

21.3 The Inflammasome Architecture​

Equation 21.1 (NLRP3 Assembly): NLRP3+ASC+Pro-caspase-1→Active complex\text{NLRP3} + \text{ASC} + \text{Pro-caspase-1} \rightarrow \text{Active complex}

Pattern recognition driving assembly.

21.4 The mTORC Complexes​

Definition 21.2 (Nutrient Sensing): mTORC1=mTOR+Raptor+mLST8+Others\text{mTORC1} = \text{mTOR} + \text{Raptor} + \text{mLST8} + \text{Others}

Metabolic decision center.

21.5 The COP9 Signalosome​

Theorem 21.2 (Deneddylase Activity): CSN+Neddylated CRL→Deneddylation\text{CSN} + \text{Neddylated CRL} \rightarrow \text{Deneddylation}

Regulating E3 ligase activity.

21.6 The Cooperative Assembly​

Equation 21.2 (Nucleation-Elongation): d[Complex]dt=kn[M]n+k+[Seed][M]\frac{d[\text{Complex}]}{dt} = k_n[\text{M}]^n + k_+[\text{Seed}][\text{M}]

Two-phase assembly kinetics.

21.7 The Threshold Behavior​

Definition 21.3 (Ultrasensitive Response): Output=[Input]nKn+[Input]n\text{Output} = \frac{[\text{Input}]^n}{K^n + [\text{Input}]^n}

Sharp transitions in activation.

21.8 The Prion-like Domains​

Theorem 21.3 (Polymerization Motifs): Low complexity→Higher-order assembly\text{Low complexity} \rightarrow \text{Higher-order assembly}

Self-templating assembly.

21.9 The Liquid Droplets​

Equation 21.3 (Phase Separation): c>ccritical⇒Condensate formationc > c_{\text{critical}} \Rightarrow \text{Condensate formation}

Signalosomes as biomolecular condensates.

21.10 The Signal Integration​

Definition 21.4 (Multi-input Processing): Decision=f(Input1,Input2,...,Inputn)\text{Decision} = f(\text{Input}_1, \text{Input}_2, ..., \text{Input}_n)

Boolean logic in molecular form.

21.11 The Disassembly Control​

Theorem 21.4 (Signal Termination): DUBs/Phosphatases→Complex dissolution\text{DUBs/Phosphatases} \rightarrow \text{Complex dissolution}

Active disassembly mechanisms.

21.12 The Decision Principle​

Signalosomes embody ψ's principle of collective decision-making—individual proteins voting through binding, the assembly processing information to reach cellular verdicts that determine fate.

The Signalosome Equation: ψoutput=Θ(∑iwi⋅Inputi−Threshold)\psi_{\text{output}} = \Theta\left(\sum_i w_i \cdot \text{Input}_i - \text{Threshold}\right)

Weighted voting creating binary decisions.

Thus: Signalosome = Assembly = Decision = Computation = ψ

"In signalosomes, ψ creates molecular parliaments—each protein a representative, their assembly a deliberation, their output a decision that can mean life or death, growth or stasis, inflammation or tolerance."